Introduction: Immune evasion of diffuse large Bcell lymphoma
(DLBCL) is one of the reasons accounting for its unsatisfactory thera-
peutic effects. Investigating the underlying mechanisms may provide
novel promising potential targets for DLBCL treatment. Exosomes are
known to play a significant role in cancer initiation and progression.
However, its role in DLBCL immune escape remains to be elucidated.
Methods: The proportion, immunophenotype and cytotoxic function
of natural killer (NK) cells in DLBCL patients were detected by flow
cytometry. Exosomes were isolated from the culture medium of
DLBCL cells and plasma of DLBCL patients by ultracentrifugation and
then were characterized by immunoblotting, NanoSight and trans-
mission electron microscopy. The role of DLBCLderived exosomes on
NK cells was assessed by immunofluorescence and flow cytometry.
Elisa, coculture experiments and immunoblotting were performed to
explore the molecular mechanisms of exosomes on NK cells.
Results: We reported the existence of NK cell exhaustion and
increased expression of Tcell immunoglobulin mucin receptor 3
(TIM3) on NK cells in DLBCL patients. Exosomes were identified in
DLBCL patient plasma and NK cell functions was negatively associ-
ated with immunosuppressive molecules levels in exosomes. And we
found that exosomes derived from DLBCL cells carried immunosup-
pressive cytokine such as transforming growth factor‐β (TGF‐β) and
lead to decreased percentage and function of NK cells. Finally, we
showed that treatment of NK cells with TGF‐β neutralizing antibody
blocked the effect of exosomes on NK cells.
Conclusions: Altogether, our findings reveal the prognostic value of
plasma exosome of DLBCL patients, provide a molecular basis
for the role of exosome in immune evasion of DLBCL and highlight the
unique function of exosome as an attractive therapeutic target.
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
300 |INTESTINAL TCELL LYMPHOMAS: MOLECULAR
INTEGRATIVE ANALYSIS RECOGNIZES DIFFERENT
THERAPEUTIC TARGETS FOR EACH SUBTYPE
R. Manso
1
, M. Rodriguez
1
, C. Chamizo
1
, N. Pérez
1
, R. AlonsoAlonso
1
,
P. A. Minguez
2
, J. Borregon
1
, E. BaezDuran
1
, E. M. Casasdel Pozo
1
,
M. A. Piris
1
, F. Rojo
1
, S. M. RodriguezPinilla
1
1
Fundación Jiménez Díaz, Pathology, Madrid, Spain,
2
Fundacion Jimenez
Diaz, Genetics and Genomics Department and Bioinformatics Unit,
Madrid, Spain
More frequent types of Primary intestinal Tcell lymphomas are
Enteropathyassociated Tcell lymphoma (EATL) and monomorphic
epitheliotropic intestinal Tcell lymphoma (MEITL). Although they
differ in epidemiology, morphology and immunophenotype they both
shared an unfavourable outcome with poor response to standard
chemotherapeutic regimens. Definition of the genetic landscape of
these tumours the data is still in process. Here we have analyzed a
series of both EATL and MEITL cases in an attempt to identify tumour
specific therapeutic targets. The series included 7 (EATL) and 9 MEITL
formalinfixed paraffinembedded (FFPE) cases. Both expression and
mutational studies were done by different platforms. GEP analysis
disclosed that the CD40pathway was statistically differentially
expressed in the EATL cases, due to the overexpression of BTG2,
HTRA1 or RUNX1 genes; moreover, TNFRSF8 was upregulated in this
group. While RPS6KA3, HDAC2 and FH were highly upregulated in the
MEILT subgroup. Other potential targets differentially expressed in
the EATL subgroup were CD274, TGFB1, SMAD3 or KDR while MEITL
cases displayed increased expression of a set of cytotoxic markers
(GNLY, NKG7 or KLRB1). A total of 24 different genes were found
mutated in the whole series of cases. The number of mutations per case
as well as the allele frequency of most of the mutations was higher in
the MEITL subgroup of tumours. Most EATL patients showed muta-
tions in DNA repair genes, followed by alterations in genes of the
NOTCH, VEGF or PI3K/AKT signaling pathways. On the contrary,
MEITL cases analysed showed mutations in SETD2 gene, the RAS gene
family or the JAK/STAT pathway. Integrative molecular analysis con-
firms that EATL and MEITL are strongly different disorders, linking
both expression signatures and mutational data. This study suggests
tumor typespecific therapeutic targets including immunotherapy for
EATL and CD30, MAPK, JAK/STAT pathways inhibitors for MEITL.
Keywords: Extranodal nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
301 |EXPRESSION OF HUMAN LEUCOCYTE ANTIGENS
GENETIC POLYMORPHISMS IN A CASE SERIES OF FIVE PATIENTS
WITH SEQUENTIAL LYMPHOMAS
E. Verrou
1
, A. Fylaktou
2
, I. Diamanti
3
, K. Tsirou
1
, T. Triantafyllou
1
,
A. Sevastoudi
1
, Z. Tsinaris
2
, G. I. Grigoriadou
1
, P. Konstantinidou
1
,
G. Gioula
4
, E. Katodritou
1
1
Theagenio Cancer Hospital, Hematology, Thessaloniki, Greece,
2
Hippokration Hospital, National Peripheral Histocompatibility Center,
Thessaloniki, Greece,
3
Theagenio Cancer Hospital, Biochemisty &
Microbiology Department, Thessaloniki, Greece,
4
Medical School, AUTH,
Microbiology, Thessaloniki, Greece
Introduction: Sequential lymphomas involving both classical Hodgkin
Lymphoma (cHL) and Primary Mediastinal Bcell Lymphoma have been
previously reported but initial diagnosis of cHL followed by a distinct
diagnosis of Diffuse Large BCell Lymphoma (DLBCL) or vice versa is an
extremely rare phenomenon. Multiple etiological factors are involved
in lymphoma pathogenesis. The major histocompatibility complex
(MHC) has been studied extensively about rising susceptibility in many
diseases and certain different human leukocyte antigen (HLA) associ-
ations with HL and DLBCL have been proposed. This is the first report
of HLA investigation in patients with sequential lymphomas.
Methods: We defined HLA class I (HLAA, HLAB, HLAC) and class II
(HLADRB1, HLADQB1) in 5 (2 female/ 3 male) patients with
sequential diagnosis of cHL and DLBCL or vice versa. HLA typing for
396
-
SUPPLEMENT ABSTRACTS
HLAA*, B*, C*, DRB1*, DQB1* was performed using SequenceSpecific
Oligonucleotide HLA typing (SSO) and SequenceSpecific Primer HLA
typing (SSP). The results of typing were compared using χ
2
to those
found by 250 healthy adult donors from the bone marrow bank of
Northern Greece.
Results: Three of our patients were HLADRB1*11 (DR11)/HLA
DQB1* 03 (DQ7) positive (5/10 haplotypes). The high frequency of
HLADR11/DQ7 combination among our patients (50%) differed not
significantly from the observed frequency of this combination among
healthy individuals (21%) (p =0.04 but after using Yate's correction
p=0.09). Τwo of our patients displaying this HLA combination were
treated with ABVD for cHD and developed DLBCL nine and three
years after diagnosis of cHL respectively. Both patients are alive and
in remission for both lymphomas. The third HLADR11/DQ7+patient
was treated with CHOP for DLBCL and developed cHL 21 years after
diagnosis of primary DLBCL. Interestingly while being in remission
for both lymphomas she additionally developed mycosis fungoides
displaying finally diagnoses of three sequential lymphomas.
Conclusions: Although not reaching statistical significance due to
small number of cases our results suggest that HLA analysis may be a
field of investigational interest regarding patients with sequential
lymphomas. HLA DR11 has been previously reported as a risk factor
for cHL irrespectively from EBV status. Importantly HLADQ7 is
involved in the pathogenesis of autoimmune diseases. Interestingly
HLADR11/DQ7 combination has been previously reported in asso-
ciation with vulvar lichen sclerosus and asthma. Of note this combi-
nation was also described in one case of familial systemic sclerosis
following exposure to organic solvent. In conclusion our results
emphasize the necessity for collecting and investigating sequential
lymphomas in order to elucidate the underlying contributory mecha-
nisms in the pathogenesis of lymphoproliferative diseases.
Keywords: Lymphoid Cancers Other, Pathology and Classification
of Lymphomas
No conflicts of interests pertinent to the abstract.
302 |IMMUNOHISTOCHEMICAL AND HISTOPATHOLOGICAL
STUDY FOR THE DIAGNOSIS AND CLASSIFICATION OF
LYMPHOMAS.
J. J. Jiménez Galainena
1
, J. Lamadrid García
1
, Z. Gutiérrez Aleaga
1
,
M. Amigó de Quesada
1
, M. Nazario Dolz
1
, L. Heredia Manzano
1
,
E. Gámez Pérez
1
, W. Marcial Martínez
1
, A. Columbié Molina
1
,
E. Gracia Medina
2
, T. González Madruga
2
, J. Peraza Bordao
3
1
National Oncology Institute, Anatomic Pathology Department, Havana
City, Cuba,
2
National Oncology Institute, Department of Clinical
Oncology, Havana City, Cuba,
2
National Oncology Institute, Department
of Clinical Oncology, Havana City, Cuba,
3
Institute of Tropical Medicine
IPK, Department of Anatomic Pathology, Havana City, Cuba
Introduction: The histopathological classification and subclassifi-
cation of lymphomas in hematopathology is the gold standard for the
diagnosis of these diseases. Different techniques, such as immuno-
histochemistry, fluorescent in situ hybridization and molecular
studies have been included in the diagnostic field of Anatomic Pa-
thology. The information obtained with these techniques combined
with conventional light microscopy study allows a specific morpho-
logical diagnosis according to the WHO Classification permitting the
best treatment in the patients.
Objective: The study with immunohistochemical techniques was to
classify and subclassify these neoplastic lymphoid processes.
Material and methods: The study included 2053 biopsies of different
sites diagnosed as lymphomas at the Pathology Department of the
National Oncology Institute, Havana City, Cuba from the period of
2007 to 2019 with a panel of different antibodies for hematolymphoid
processes employing the technique of immunohistochemistry in
paraffin blocks. The manual and automated immunohistochemical
staining were used. The visualization systems included the Polymer
Detection System and the Ultraview Universal DAB Detection Kit.
Results: The NonHodgkin´s B Cell Lymphomas were the predominant
immunophenotypic type (1478 cases)(71.9%).The B Cell Lymphomas
CD20 positive were 1311 cases (63.8 %).The Diffuse Large B Cell
Lymphomas were the most frequent histopathological type (725 cases)
(35.3%).The Diffuse Large B Cell Lymphoma molecular subtypes clas-
sification (Hans Algorithm)(CD10/Bcl6/Mum1) by immunohisto-
chemistry were the following in the cases studied (96 cases)(2015
2019): GBC (29 cases)(30.2%), ABC (45 cases)(46.8%),non GBC / non
ABC (18 cases)(18.7%), Double expressor (4 cases)(4.16%).The Pe-
ripheral T Cell Lymphomas (81 cases) and Anaplastic Large Cell Lym-
phoma(67 cases) were the principal histologies diagnosed in the group
of NonHodgkin´s T Cell Lymphomas (153 cases)(7.45%).The extra-
nodal sites were 941 cases (45.8%) and the Head and Neck location
was the common site diagnosed in this group (195 cases)(20.7%).
Conclusion: The study showed the different frequencies, locations
and histological types of the lymphomas in our daily work of a period
of time of 13 years in the Immunohistochemistry Laboratory at the
Pathology Department.
Keywords: GBC (Germinal center Bcelllike), ABC (Activated Bcell
like), non GBC / non ABC (non Germinal center Bcelllike) / (non
Activated Bcelllike)
Keywords: Pathology and Classification of Lymphomas
No conflicts of interests pertinent to the abstract.
CHRONIC LYMPHOCYTIC LEUKEMIA
303 |PROGNOSTIC VALUE OF APOLIPOPROTEIN A IN
CHRONIC LYMPHOCYTIC LEUKEMIA
X. Yun
1
, Y. Zhang
1
, X. Sun
1
, X. Hu
1
, H. Zhang
1
, Z. Yin
1
, X. Zhang
1
, M.
Liu
1
, X. Wang
1
1
Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong
University, Department of Hematology, Jinan, Shandong, China
SUPPLEMENT ABSTRACTS
-
397
Introduction: Lipid metabolism is related to lymphomagenesis and a
potential target for novel therapies of some hematologic malig-
nancies. Chronic lymphocytic leukemia (CLL) cells, like adipose cells
rather than Blymphocytes or other leukemia cells, utilize free fatty
acids to produce energy. There is a pronounced drop of high
density lipoprotein (HDL) in CLL patients 34 years before the
diagnosis. Apolipoprotein A, the major structural protein of HDL,
takes effect on lipid transportation and immunity. Nevertheless, the
role of ApoA in CLL has not been explored. This study aimed to
investigate the potential role of ApoA in the prognosis of CLL
patients.
Methods: A total of 150 newly diagnosed CLL patients from January
2010 to December 2019 in Shandong Provincial Hospital were
enrolled in this study. KaplanMeier curves and univariate and
multivariate Cox proportion hazard regression models were per-
formed to evaluate the prognostic value of ApoA. Pearson tests,
Spearman tests and Chisquare tests were performed to evaluate the
correlation between ApoA and other clinical and laboratory
parameters.
Results: KaplanMeier curves revealed that increased ApoA was
associated with longer overall survival (OS) (χ
2
=14.985; p<0.001;
shown in Figure 1A) and progressionfree survival (PFS) (χ
2
=
FIGURE 1 KaplanMeier curves of Apolipoprotein A (ApoA) of overall survival (OS) and progressionfree survival (PFS) of chronic
lymphocytic leukemia (CLL) patients. (A) Increased ApoA was associated with longer OS of CLL patients. (B) Increased ApoA was longer PFS of
CLL patients. (C) Increased AopA posttherapy was associated with longer OS of CLL patients. (D) Increased AopA posttherapy was
associated with longer PFS of CLL patients
398
-
SUPPLEMENT ABSTRACTS
16.190; p<0.001; shown in Figure 1B). Univariate and multivariate
Cox regression revealed that ApoA was a significant independent
prognostic biomarker of OS (p=0.028) and PFS (p<0.001). The
level of ApoA did not change with treatment. However, ApoA
levels of CLL patients after therapy were also correlated to OS (χ
2
=
6.732; p=0.009; shown in Figure 1C) and PFS (χ
2
=8.822;
p=0.003; shown in Figure 1D). The low level of ApoA was related
to the advanced stages (p<0.001) and increased β2microglobulin
(r=0.447, p<0.001), which was known poor prognostic factors
in CLL.
Conclusions: Our study reveals that ApoA is a favorable prognostic
biomarker of OS and PFS in CLL for the first time. The novel prog-
nostic biomarker may increase prognostic accuracy of CLL.
The research was funded by: National Natural Science Foundation
(No.82000195, No.82070203, No.81770210, No.81473486 and
No.81270598); Key Research and Development Program of Shandong
Province (No.2018CXGC1213); Technology Development Projects of
Shandong Province (No.2017GSF18189); Translational Research
Grant of NCRCH (No.2021WWB02, No.2020ZKMB01); Shandong
Provincial Natural Science Foundation (No.ZR2020QH094); Taishan
Scholars Program of Shandong Province; Shandong Provincial Engi-
neering Research Center of Lymphoma; Academic Promotion Pro-
gramme of Shandong First Medical University (No. 2019QL018;
No.2020RC007); Technology Development Project of Jinan City
(No.200027182); Shandong Provincial Hospital Youth Talent Plan;
Shandong Provincial Hospital Research Incubation Fund.
Keywords: Diagnostic and Prognostic Biomarkers, Chronic Lympho-
cytic Leukemia (CLL)
No conflicts of interests pertinent to the abstract.
304 |TIME TO HEMATOLOGIC RECOVERY PREDICTS
SURVIVAL IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
TREATED WITH FLUDARABIN, CYCLOPHOSPHAMIDE AND
RITUXIMAB 11 YEARS OF REALWORLD EXPERIENCE
A. V. Mata
1
, I. P. Mesquita
1
, D. Alves
1
, J. Medeiros
1
, B. Polo
1
, C.
Lopes
1
, M. J. Costa
1
, C. Martins
1
, G. Esteves
1
, J. F. Lacerda
1
, J.
Raposo
1
1
Hospital Santa Maria, Centro Hospitalar Universitário Lisboa Norte,
Hematology and Bone Marrow Transplant Department, Lisbon, Portugal
Introduction: Chemotherapyfree regimens are frequently the first
choice in chronic lymphocytic leukemia/small lymphocytic lym-
phoma (CLL/SLL) treatment. Despite some concerns about short
and longterm toxicity, chemotherapy is still a highly valuable
option in a specific subset of patients. We wanted to assess effi-
cacy, overall and progression free survival (OS and PFS), short and
longterm toxicity and predictors of response in the reallife
setting.
Methods: Unicentric, retrospective study of CLL/SLL patients treated
with fludarabin, cyclophosphamide, rituximab (FCR) from July 2008
until April 2019.
Results: Sixtynine patients were included, 74% were male, median
age of 58 year (IQR 5063). Seventyeight percent were treated in
first line setting, 22% had relapsed/refractory (R/R) disease. Before
treatment, FISH analysis was performed in 67 patients: 4.5% had
(del)17p, 14.9% had del(11q), 37.3% had (del)13q, 28.4% had
triss12 and 29.9% had normal cytogenetic analysis. We found 2/45
patients with TP53 mutation and 19/39 patients had mutated
IgHV.
Complete response (CR) was reached in 41.8%, CR with incom-
plete marrow recovery in 34.3%, partial response in 13.4%, stable
and progressive disease in 3% and 7.5%, respectively. Minimal re-
sidual disease (MRD) was negative in 19/33 patients.
Median followup of 59.6 months, 1st line median PFS of 55.3
months and median OS not reached, with 80.2% of patients alive at
median follow up time. On the R/R setting, median PFS and OS were
41.5 and 58.3 months respectively. Negative MRD had a positive
impact on survival (median PFS not reached vs. 31.3 M, p =0.015), as
well as cytogenetic analysis (p =0.003).
Half of the patients received 6 cycles and more than 75% received at
least 4 cycles. Dose reduction was needed in 18% of the patients, and
36% had some delay in treatment schedule. Hematologic toxicity
grade 3 was found in 62%: anaemia 4.3%, neutropenia 49%,
thrombocytopenia 24.6%.
Nearly half had complete hematologic recovery (49.7%) with median
time to recovery of 124 days. Of note, PFS was longer in patients
who took more than 124 days for hematologic recovery (median PFS
110.9 vs 42.7 months, p <0.001; Fig 1).
Infeccious adverse events grade 3 were found in 7.5% of patients,
and 17.4% of opportunistic infections (epsteinbarr, herpes zoster, P.
jiroveci). Second neoplasms were found in 13% of patients: 2 acute
FIGURE 1 Time to hematologic recovery (HR) predicts
progression free survival
SUPPLEMENT ABSTRACTS
-
399
leukemias, 3 adenocarcinomas and 4 skin neoplasms. There were 20
fatalities: 9 for progressive disease (median time to death 49
months), 3 for infectious adverse events (1720 days after treat-
ment), 3 for 2
nd
neoplasms and 5 patients for nonrelated causes.
Conclusions: In the realworld setting with a long follow up time, FRC
attained 76% of CR in 1st line therapy, with long lasting remissions
and an acceptable toxicity profile. Cytogenetic analysis, negative
MRD and, interestingly, longer time to hematologic recovery had a
positive impact in PFS.
EA previously submitted to regional or national meetings (up to
1000 attendees).
Keywords: Diagnostic and Prognostic Biomarkers, Late Effects in
Lymphoma Survivors, Chronic Lymphocytic Leukemia (CLL)
No conflicts of interests pertinent to the abstract.
305 |FACILITATED IMMUNOGLOBULIN (fSCIG) USE IN
PATIENTS WITH SECONDARY IMMUNODEFICIENCY DISEASES:
TWOYEAR INTERIM RESULTS FROM THE FIGARO STUDY
M. Dimou
1
, D. Huscher
2
, C. Hermann
3
, D. Pittrow
4
, M. Speletas
5
,
M. Borte
6
1
National & Kapodistrian University of Athens Medical School, First
Department of Propaedeutic Internal Medicine, Athens, Greece,
2
Charité
Universitätsmedizin Berlin, Institute of Biometry and Clinical
Epidemiology, Berlin, Germany,
3
Baxalta Innovations GmbH, Global
Medical Affairs, Vienna, Austria,
4
Technical University of Dresden,
Institute for Clinical Pharmacology, Medical Faculty, Dresden, Germany,
5
University of Thessaly, School of Health Sciences Faculty of Medicine,
Department of Immunology and Histocompatibility, Thessaly, Greece,
6
St. Georg Hospital, Hospital for Children and Adolescents, Leipzig,
Germany
Introduction: Secondary immunodeficiency diseases (SID) commonly
affect patients with hematological malignancies such as chronic
lymphocytic leukemia (CLL) and lymphoma. Immunoglobulin
replacement therapy (IGRT) is an important therapeutic option for
preventing severe, recurrent, or persistent infections in patients with
hematologic malignancies and SID. Facilitated subcutaneous immu-
noglobulin (fSCIG) is a dualvial unit of immunoglobulin G (IgG) 10%
and recombinant human hyaluronidase (rHuPH20) approved in the
European Union as an IGRT for patients with SID. rHuPH20 de-
polymerizes hyaluronan in the extracellular matrix to transiently in-
crease local subcutaneous tissue permeability, allowing for fSCIG
infusion at rates, volumes, and frequencies comparable to intrave-
nous immunoglobulin (IVIG) with better systemic tolerability. This
study assesses fSCIG usage and tolerability over time in patients with
SID seen in routine clinical practice.
Methods: FIGARO (NCT03054181) is a European multicenter,
prospective, observational study. Patients were eligible if they
received 1 fSCIG infusion for primary immunodeficiency diseases
or SID and provided informed consent. Patients are being followed
for up to 3 years. An interim analysis (data cutoff date: February
2, 2021) was conducted to evaluate fSCIG usage and tolerability
over the first 2 years of follow up in the subgroup of patients with
SID.
Results: Of the 156 patients enrolled, 31 (mean [range] age: 61
[3–88] y) had SID and are included in the baseline (inclusion visit)
analysis. At interim analysis, 1and 2year followup data were
available for 23 and 12 patients, respectively. Indications for IGRT
were CLL (n =20), nonHodgkin lymphoma (n =6), SID due to
immunosuppressive therapy (n =3), and Hodgkin lymphoma (n =2).
At the inclusion visit, fSCIG (median total monthly dose: 30.0 g) was
most recently infused at home (61%) or at a hospital (36%) by the
patient (58%) or a nurse (42%). Most patients received fSCIG
every 4 weeks (68%), infused into a single site. The median
maximum infusion rate was consistent over the 2year follow
up: 290 mL/h at inclusion, 268 mL/h at 1 year, and 300 mL/h at 2
years. The median infusion volume was 300 mL across all visits to 2
years, with all patients receiving the full dose as planned. Two pa-
tients each reported 1 adverse drug reaction (ADR; erythema
and headache) at the inclusion visit, with no ADRs reported at
any of the followup visits. One patient changed to IVIG by 12
months.
Conclusions: In patients with SID primarily due to hematologic ma-
lignancies, fSCIG was tolerated over 2years' follow up in routine
clinical practice and offered the flexibility of administration at home
or in a hospital setting, either by the patient or a nurse. Infusion
parameters remained consistent over time.
EA previously submitted to EHA 2021.
The research was funded by: Baxalta Innovations GmbH, a Takeda
company, funded this study. Baxalta US Inc., a Takeda company,
funded writing support.
Keywords: Immunotherapy, Ongoing Trials
Conflicts of interests pertinent to the abstract
Dör. Huscher
Educational grants: has received travel compensation from Actelion
Pharmaceuticals, Switzerland, BoehringerIngelheim, Germany, and
Shire
C. Hermann
Employment or leadership position: an employee of the Baxalta In-
novations GmbH, a member of the Takeda group of companies
Stock ownership: a Takeda stock owner
D. Pittrow
Consultant or advisory role: has acted as consultant for Baxalta
Other remuneration: reports personal fees from Actelion, Bayer,
Aspen, Boehringer Ingelheim, Sanofi, Biogen, and MSD
400
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SUPPLEMENT ABSTRACTS
M. Speletas
Research funding: institution has received a research grant from Shire
M. Borte
Consultant or advisory role: has participated in advisory boards for
CSL Behring, Octapharma, and Shire
Research funding: institution has received research grant support
from CSL Behring, Octapharma, and Baxalta
306 |EFFECTIVENESS OF THERAPY WITH FLUDARABINE,
CYCLOPHOSPHAMIDE AND RITUXIMAB (FCR) FOR PATIENTS
WITH CHRONIC LYMPHOCYTIC LEUKEMIA
I. Kogarko
1
, A.K. Golenkov
2
, E.V. Kataeva
2
, B.S. Kogarko
1
, I.I. Ganeev
1
1
Institute of Chemical Physics, RAS, Chembio Processes, Moscow, Russian
Federation,
2
M.F. Vladimirsky Moscow Regional Research and Clinical
Institute (MONIKI), Immunology and Hematology, Moscow, Russian
Federation
Goals: an evaluation of effectiveness of Fludarabine, Cyclo-
phosphomide and Rituximab (FCR therapy) for patients with newly
diagnosed Chronic Lymphocytic Leukemia (CLL) for validation of
results from multicentered clinical trials in real clinical practice.
Materials and methods: sixty six (66) patients with newly diagnosis
of CLL were included to this prospective study with average age of
58 years old (3973 years old). Stage I II according to Rai staging
system was found in 76% of patients; Stage IIIIV in 24 % of pa-
tients. All patients received 68 cycles of inductive FCR therapy:
Rituximab 375 mg/m
2,
iv first cycle, followed by 500 mg/m
2,
iv;
Fludarabine 25 mg/m
2,
iv days 2,3 and 4 of a cycle; Cyclophos-
phamide 250 mg/m
2
,iv– days 2,3 and 4 of a cycle). Patients were
divided into two groups based on duration of induction cycles (IC).
Group 1 had average IC of 36 days; Group 2 49 days. Evaluation of
immunochemotherapy effectiveness was determined by presence of
remissions (IWCLL2008), progressionfree survival (PFS) and overall
survival (OS) (Kaplan Meier method).
Results: Complete Remission (CR) was observed more often in Group
1 (FCR36) than in Group 2 (FCR49) 56.6% and 37.9% of patients,
respectively (p >0.05). Median PFS was 36 months in all patients; 45
months in Group 1 (FCR36) and was not achieved in Group 2
(FCR49). Median OS was 45 months in Group 1 (FCR36) and was
not achieved in Group 2 (FCR49).
Conclusions: confirmation of FCR therapy effectiveness for newly
diagnosed CLL patients was established in real clinical practice
characterized by nonselective patient groups and prolonged induc-
tion therapy cycles. Results of this study provide validation for re-
sults from multicentered clinical trials and could be reproduced on a
greater scale in clinical practice.
Keywords: Chronic Lymphocytic Leukemia (CLL), Chemotherapy,
Immunotherapy
No conflicts of interests pertinent to the abstract.
307 |EFFECTIVENESS AND SAFETY OF IBRUTINIB IN
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) AND MANTLE CELL
LYMPHOMA (MCL) IN BELGIAN ROUTINE CLINICAL PRACTICE
WITH A 3YEAR FOLLOWUP
A. Janssens
1
, S. Snauwaert
2
, D. Bron
3
, Z. Berneman
4
, F. Offner
5
,
C. Van Bogaert
6
, B. De Beleyr
7
, A. Smet
8
, L. Nielsen
9
, R. Wapenaar
10
,
M. André
11
1
Universitair Ziekenhuis Leuven, Department of Hematology,
Leuven, Belgium,
2
AZ SintJan Brugge, Department of Hematology,
Brugge, Belgium,
3
Institut Jules Bordet (ULB), Department of
Hematology, Brussels, Belgium,
4
Universitair Ziekenhuis Antwerpen,
Department of Hematology, Edegem, Belgium,
5
Universitair Ziekenhuis
Gent, Department of Hematology, Gent, Belgium,
6
JanssenCilag NV,
Medical Affairs, Beerse, Belgium,
7
JanssenCilag NV, Medical Affairs,
Beerse, Belgium,
8
JanssenCilag NV, Market Access, Beerse, Belgium,
9
JanssenCilag NV, Medical Affairs, Beerse, Belgium,
10
JanssenCilag
BV, Statistics Department, Breda, Netherlands,
11
Université Catho-
lique de Louvain, CHU UCL Namur, Department of Hematology, Yvoir,
Belgium
Introduction: The Belgian ibrutinib RealWorld (RW) Data (BiRD)
study is a multicenter, observational study of adults with CLL, MCL, or
Waldenström's macroglobulinemia. The RW study aims to assess
ibrutinib outcomes (primary: progressionfree survival [PFS] and
overall response rate [ORR]; secondary: included overall survival [OS]
and safety) in patients (pts) with previously untreated or relapsed or
refractory (R/R) CLL and R/R MCL in Belgium. Here we present results
from the third interim analyses (IA) with a median followup of 34.3
months for the CLL cohort and 35.8 months for the MCL cohort.
Methods: Data were collected both prospectively (pro) and retro-
spectively (ret). Total population results were adjusted for left
truncation.
Results: Effectiveness results are presented in the Table.
In the CLL cohort, 221 pts (pro n =71; ret n =150) were
included in the effectiveness population; 64.3% were male, median
age at ibrutinib initiation was 72 (range, 3890) years (y), median time
from diagnosis to ibrutinib initiation was 5.8 y, 27.4% were previously
untreated, 59.1% had del17p and/or TP53 mutation, and 72.5% had
no IGHV mutation. ORR was 90.0% (complete response [CR] 16.7%,
partial response [PR] 51.6%, PR with lymphocytosis 21.7%). Of
226 pts in the CLL safety population, 96.9% had 1 treatment
emergent adverse event (TEAE) and 52.2% had 1 serious TEAE.
TEAEs led to dose reduction, interruption, or discontinuation in
21.2%, 31.9%, and 26.5% of pts, respectively. TEAEs of interest
reported as % (% difference from second IA, after an additional
15.3 mos of followup) were: major bleeding 4.9% (0.4%); infection
66.4% (9.3%); hypertension 17.3% (5.1%); atrial fibrillation (AF)
10.6% (3.2%); arthralgia/myalgia 16.8% (4.1%); diarrhea 21.7%
SUPPLEMENT ABSTRACTS
-
401
(3.2%). Median treatment duration for pts with CLL was 25.5 mos
(19.6/28.6 mos pro/ret), and 135/226 pts (58.7%) remain on
treatment.
In the MCL cohort, 76 pts (pro n =20; ret n =56) were included in
the effectiveness population; 76.3% were male, median age at ibrutinib
initiation was 74 (range, 4788) y, and median time from diagnosis to
ibrutinib initiation was 2.8 y. ORR was 93.4% (CR 39.5%, PR 53.9%). Of
76 pts in the MCL safety population, all had 1 TEAE and 67.1% had 1
serious TEAE. TEAEs led to dose reduction, interruption, or discon-
tinuation in 31.6%, 43.4%, and 26.3% of pts, respectively. TEAEs of
interest reported as % (% difference from second IA, after an additional
15.2 mos of followup) were: major bleeding 7.9% (1.3%); infection
64.5% (6.6%); hypertension 6.6% (0%); AF 21.1% (4.0%); arthralgia/
myalgia 11.8% (0%); diarrhea 35.5% (5.2%). Median treatment dura-
tion for pts with MCL was 24.7 mos (22.8/25.3 mos pro/ret), and 26/76
pts (34.2%) remain on treatment.
Conclusions: Results from the BiRD study confirm the sustained
effectiveness of ibrutinib in both CLL and MCL. TEAEs were
manageable in elderly pts with no new safety signals.
EA previously submitted to EHA 2021.
The research was funded by: Janssen Pharmaceutica NV, and Phar-
macyclics LLC, an AbbVie Company.
Keywords: Chronic Lymphocytic Leukemia (CLL), Indolent non
Hodgkin lymphoma, Molecular Targeted Therapies
Conflicts of interests pertinent to the abstract
A. Janssens
Consultant or advisory role: Janssen, Roche, Gilead, Abbvie, Novartis,
Amgen, SanofiGenzyme
Honoraria: Janssen, Roche, Abbvie, Novartis, Amgen, Sanofi
Genzyme, Celgene
Research funding: Janssen
Educational grants: Janssen, Celgene, Abbvie, Roche
D. Bron
Consultant or advisory role: Janssen
Honoraria: Janssen
Research funding: Janssen
F. Offner
402
-
SUPPLEMENT ABSTRACTS
Research funding: Janssen
C. Van Bogaert
Employment or leadership position: Janssen
B. De Beleyr
Employment or leadership position: Janssen
Stock ownership: Janssen, Pfizer
A. Smet
Employment or leadership position: Janssen
L. Nielsen
Employment or leadership position: Janssen
R. Wapenaar
Employment or leadership position: Janssen
Stock ownership: J&J
M. André
Consultant or advisory role: Takeda, BristolMyersSquibb, Kar-
yopharm, Gilead, Incyte
Research funding: Roche, Johnson & Johnson, Takeda
Educational grants: Roche, BristolMyersSquib, Celgene, Gilead,
Abbvie
308 |HEMORRHAGIC MANIFESTATIONS OF LONG TIME
ANTICOAGULANTS TREATMENT IN PATIENTS WITH CHRONIC
LYMPHOCYTIC LEUKEMIA RECIVING IBRUTINIB.
E. Emelina
1
, G. Gendlin
1
, I. Nikitin
1
1
Pirogov Russian National Research Medical University, Hospital Therapy
2, Moscow, Russian Federation
Introduction. Longterm use of anticoagulants (AC) for atrial fibril-
lation (AF) in patients (pts) with chronic lymphocytic leukemia (CLL)
in the setting of ibrutinibassociated thrombocytopathy (Ib), throm-
bocytopenia and platelet variability is associated with a particular
risk of hemorrhagic hemorrhage complications.
Method. We have observed in dynamics for 5 years 217 pts with CLL
constantly receiving Ib. AF occurred in 39 pts (19.9%) during treatment
Ib, 21 pts had AF before Ib. 46 pts with CLL and AF received AC from 12
to 58 months, of which 19 women aged 70.0 (64.074.0) years and 27
men aged 67.5 (63.570.0) years. 20 pts receive apixaban (api), 20
rivaroxaban (riva), 6 dabigatran (dabi). We tracked all emerging hem-
orrhagic manifestations in pts with CLL, taking AC. During the period of
use of AC, the influence of platelet level and variability on the occur-
rence of hemorrhages in these pts was evaluated.
Results. In 65.9% of pts with CLL receiving Ib and AC hemorrhages
persist throughout the observation period, represented by nosebleeds
(34.5%), hemorrhage in the sclera of the eye (27.6%), gross hematuria
(20.7%), gingival bleeding (13.8%), hematomas (75.9%), petechiae
(10.3%), bleeding from a rectal tumor in 2 pts, hemorrhage in the
anterior chamber of the eye in 1 pts. Macrohematuria required
discontinuation of AC for up to 2–3 weeks and transfer to the minimum
dose api. In one pts with recurrent macrohematuria AC was canceled.
Hemorrhage in the sclera of the eye required outpatient ophthalmic
treatment without withdrawal of AC. Nosebleeds were recurrent and
led to the transfer of pts to the minimum dose api. Hematomas were
permanent, with predominant localization on the arms and legs, in 1 pts
they appeared on the face, neck, tongue. Several types of hemorrhages
were observed in 47.7% of patients. Transfer to the minimum dose api
2.5 mg * 2 times a day was required in 38.6% of patients due to
recurrent nosebleeds, gross hematuria, combined hemorrhages. Clin-
ically significant hemorrhages occurred less frequently in patients
treated with api compared with riva (p =0.019). We did not observe the
influence of the level and variability of platelets on the occurrence of
hemorrhages in pts with CLL receiving AC. Hemorrhages did not lead
to dose changes and withdrawal of Ib.
Conclusions. With longterm use of AC in pts with CLL and AF, among
clinically significant hemorrhages, recurrent nosebleeds, recurrent
hemorrhages in the sclera of the eye and gross hematuria prevailed,
which led to a change in the tactics of using AC. Due to hemorrhages
38.6% of pts with CLL required transfer to the minimum api dose.
Shortterm discontinuation of AC required pts with gross hematuria.
The level of platelets and their variability in our study did not have a
significant effect on the occurrence of hemorrhages. Hemorrhages did
not lead to dose reduction and withdrawal of Ib.
Keywords: Chronic Lymphocytic Leukemia (CLL)
No conflicts of interests pertinent to the abstract.
309 |INFLUENCE OF ACTIVE CARDIOMONITORING ON THE
OVERALL SURVIVAL OF PATIENTS WITH CHRONIC
LYMPHOLEUKEMIA RECEIVING IBRUTINIB.
E. Emelina
1
, G. Gendlin
1
, I. Nikitin
1
1
Pirogov Russian National Research Medical University, Hospital Therapy
2, Moscow, Russian Federation
Introduction: overall survival of patients (pts) with chronic lympho-
cytic leukemia (CLL) depends not only on the severity of the CLL, the
anticancer therapy used and the comorbidity of pts. The most
important role in the management of these pts is played by the su-
pervision of a cardiologist.
Methods: we examined and observed in dynamics for 5 years 217 pts
with CLL, constantly receiving ibrutinib, which induces arterial hy-
pertension (AH) and atrial fibrillation (AF) in a part of the pts. All pts
underwent echocardiography (ECHO), 24hour Holter ECG moni-
toring (HM), assessment of comorbidity using the Charlson index and
screening of fragility using the G8 questionnaire. Daily measurement of
blood pressure, heart rate in the morning and in the evening with
keeping a diary of measurements, was recommended for all pts, but
only 81 pts were performed, who constantly contacted us remotely
using instant messengers and made up an active cardiac monitoring
SUPPLEMENT ABSTRACTS
-
403
group. Correction of treatment was carried out in accordance with
these data.
Results: a study of the overall survival of patients with CLL receiving
ibrutinib, depending on cardiac monitoring, was carried out, starting
from the first visit. The age of pts in the active cardiac monitoring
group (n =81) and in the rest of pts (n =136) did not differ and
amounted to 66.0 (60.070.0) years and 66.0 (59.074.0) years
respectively. The number of men and women in the groups was
comparable. In the active cardiac monitoring group, there were
significantly more pts with AH 86.5% and with AF 42.7%
compared to 50.4% with AH and 15.9% with AF in the remaining pts
(p <0.0001 in both cases) and a comparable number of pts with
coronary artery disease. According to screening HM, there were
more pts with short episodes of AF in the active cardiac monitoring
group 31.4% versus 8.0% in the rest of the pts (p <0.0001).
Accordingly, the number of pts receiving cardiac treatment in the
active cardiac monitoring group was 87.6%, the rest was 53.6%
(p <0.0001). ECHO parameters did not differ in the groups. In-
dicators that significantly affect survival in the general group
(Charlson index, scores of the G8 questionnaire) did not have signif-
icant differences in the active cardiac monitoring group and in other
pts with CLL. The groups also did not differ in hematological status
and the number of cases of second tumors. Despite a significantly
more pronounced cardiac comorbidity, CLL pts under active cardiac
monitoring, including continuous remote monitoring, demonstrated
better survival compared to other patients (p <0.0001).
Conclusions: carrying out active cardiac monitoring, including con-
stant remote observation, allows achieving higher overall survival
rates for CLL pts, despite the more severe cardiac status compared to
other patients under the periodic supervision of a cardiologist.
Keywords: Cancer Health Disparities
No conflicts of interests pertinent to the abstract.
INDOLENT LYMPHOMAS
310 |INDUCTION R
2
FOLLOWED BY MAINTENANCE IN
PATIENTS WITH RELAPSED/REFRACTORY TRANSFORMED
FOLLICULAR LYMPHOMA: INTERIM ANALYSIS FROM THE
PHASE 3B MAGNIFY STUDY
F. Lansigan
1
, V. Parameswaran
2
, A. Yacoub
3
, C. M. Reynolds
4
,
S. H. Shao
5
, S. G. Moore
6
, M. Coleman
7
, D. J. Andorsky
8
, G. S.
Nowakowski
9
, M. J. Rummel
10
, J. Li
11
, J. R. Ahn
12
, M. Gharibo
12
,
J. P. Sharman
13
1
DartmouthHitchcock Medical Center, Division of Hematology and
Oncology, Lebanon, New Hampshire, USA,
2
Avera Research Institute,
Hematology, Transplantation, and Oncology, Sioux Falls, South
Dakota, USA,
3
University of Kansas Cancer Center, Department of
HematologyOncology, Westwood, Kansas, USA,
4
IHA Hematology
Oncology Consultants, Ann Arbor, Ypsilant, Michigan, USA,
5
Compass
Oncology, Rose Quarter Cancer Center, Portland, Oregon, USA,
6
UNC REX
Cancer Center, REX Hematology Oncology Associates, Raleigh, North
Carolina, USA,
7
Clinical Research Alliance Inc, Weill Cornell Medicine,
New York, New York, USA,
8
Rocky Mountain Cancer Centers, US
Oncology Research, Boulder, Colorado, USA,
9
Mayo Clinic, Division of
Hematology, Rochester, Minnesota, USA,
10
JustusLiebig Universität,
Med. Clinic IV, Hematology, Giessen, Germany,
11
Bristol Myers Squibb,
Global Biometrics and Data Sciences, Princeton, New Jersey, USA,
12
Bristol Myers Squibb, US Medical Affairs Hematology, Princeton, New
Jersey, USA,
13
Willamette Valley Cancer Institute and Research Center,
US Oncology Research, Eugene, Oregon, USA
Background: The lenalidomide +rituximab (R
2
) combination has
shown complementary clinical activity and is tolerable in both
untreated and relapsed or refractory (R/R) patients with indolent
nonHodgkin lymphoma (iNHL). Few patients with iNHL, 2%
per year (Link et al. J Clin Oncol. 2013), experience transformation
to aggressive lymphoma, ie, transformed follicular lymphoma (tFL).
Methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865)
in patients with R/R FL grades 1—3b, tFL, marginal zone lymphoma,
and mantle cell lymphoma. Lenalidomide 20 mg on d 1—21 of a 28d
cycle +rituximab 375 mg/m
2
/wk cycle 1 and then every 8 wk
starting with cycle 3 (R
2
) is given for 12 cycles followed by
1:1 randomization in patients with stable disease, partial response, or
complete response/complete response unconfirmed (CR/CRu) to R
2
vs rituximab maintenance for 18 mo. The primary end point is pro-
gressionfree survival (PFS) by 1999 International Working Group
(IWG) criteria. Secondary end points include safety, CR rate, duration
of response, duration of CR (DOCR), timetoresponse, timetonext
antilymphoma therapy, and overall survival. This analysis evaluates
the interim primary endpoint of overall response rate (ORR) by 1999
IWG criteria and safety of R
2
induction in patients with tFL in the
induction intentiontotreat population.
Results: As of August 28, 2020, 14 patients with tFL were enrolled
(median age, 70.5 y [range, 42—83]); 93% had stage III/IV disease, and
64% had bulky disease (>7 cm or >3 cm 3 lymph nodes). All patients
received prior rituximabcontaining therapy. Median number of prior
antilymphoma treatments was 2 (range, 1—7). Seven patients (50%)
had disease progression from FL 24 mo after any prior treatment.
Median time from initial FL to tFL diagnosis was 29.2 mo (range, 0—
212.1). Median followup was 37.1 mo for patients still alive; 8 pa-
tients (57%) have died, 7 from PD and 1 from adverse event (AE; res-
piratory arrest). Median duration of R
2
treatment during induction was
7.38 mo (range, 1.5—11.3). ORR was 50% (n =7), with 3 patients (21%)
having a CR/CRu. Median DOCR was not reached (95% CI, 2.8—NR),
and median PFS was 7.5 mo (95% CI, 2.6—32.5). The most common
treatment emergent AEs (TEAE) of any grade were (n, %) diarrhea (7,
50%), nausea (7, 50%), neutropenia (7, 50%), constipation (6, 43%),
fatigue (6, 43%), cough (5, 36%), decreased appetite (5, 36%), and hy-
pokalemia (5, 36%). Grade 3/4 TEAEs occurring in >1 patient included
neutropenia (6, 43%), pneumonia (3, 21%), hypokalemia (3, 21%),
leukopenia (2, 14%), and hypertension (2, 14%). Nine patients (64%)
discontinued induction lenalidomide (7 for PD and 2 withdrawals by
patient), and 5 (36%) entered maintenance treatment.
404
-
SUPPLEMENT ABSTRACTS
Conclusions: R
2
has activity in tFL. Although there were frequent
early progressions, patients who achieve CR or partial response may
have prolonged responses.
The research was funded by: Bristol Myers Squibb
Keywords: Aggressive Bcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
F. Lansigan
Consultant or advisory role: Celgene/BMS
Honoraria: Celgene/BMS
Research funding: Acrotech Pharmaceuticals
A. Yacoub
Other remuneration: SPEAKER'S BUREAU: Incyte
M. Coleman
Stock ownership: immunomedics
Research funding: Abbvie, Bristol Myers, Celgene, Genentech, Gilead,
BeiGene, Innocare, Merck, Pfizer, Roche,
D. J. Andorsky
Consultant or advisory role: Abbvie, BMS
Research funding: Celgene, AstraZeneca, Epizyme
G. S. Nowakowski
Consultant or advisory role: Selvita, Debiopharm Group, Kite/Gilead,
Celgene, MorphoSys, Genentech
Research funding: Celgene, NanoString Technologies, MorphoSys
J. Li
Employment or leadership position: BMS
Stock ownership: BMS
Research funding: BMS
Educational grants: BMS
J. R. Ahn
Stock ownership: BMS
M. Gharibo
Stock ownership: BMS
J. P. Sharman
Consultant or advisory role: Abbvie; Acerta Pharma; BMS; Celgene;
Pharmacyclics; TG Therapeutics
Research funding: Acerta Pharma; Celgene; Pharmacyclics; TG
Therapeutics
311 |AUTOLOGOUS HEMATOPOIETIC STEM CELL
TRANSPLANTATION IN FOLLICULAR LYMPHOMA IN THE ERA
OF NOVEL THERAPIESA RETROSPECTIVE ANALYSIS BY POLISH
LYMPHOMA RESEARCH GROUP.
A. T. SzlauerStefańska
1
, W. Sawicki
2
, E. PaszkiewiczKozik
3
,
J. RomejkoJarosińska
3
, T. Czerw
1
, S. Giebel
1
1
Maria SkłodowskaCurie National Research Institute of
Oncology, Department of Bone Marrow Transplantation and
OncoHematology, Gliwice, Poland,
2
Military Institute of Medicine,
Department of Internal Medicine and Hematology, Warsaw, Poland,
3
Maria SkłodowskaCurie National Research Institute of Oncology
(MSCNRIO) in Warsaw, Department of Lymphoid Malignancies, Warsaw,
Poland
Introduction: Autologous hematopoietic stem cell transplantation
(autoHSCT) in follicular lymphoma (FL) is a therapeutic option
for patients with relapsed or refractory (r/r) disease. With
the universal access to rituximab and the advent of novel ther-
apies, the role of autoHSCT remains to be reestablished.
We have performed a retrospective analysis to identify fac-
tors affecting the outcome of autoHSCT in r/r FL in the rituximab
era.
Methods: The study included 66 consecutive patients (39 women)
with r/r FL and a history of rituximab treatment. Median age was 51
years (range 2273). Median number of prior lines of systemic
therapy was 2 (17). Patients underwent autoHSCT in 3 centres
from the Polish Lymphoma Research Group in years 20002019.
Individuals with grade G3b FL or transformation to aggressive
lymphoma were excluded. Complete response was achieved before
autoHSCT in 46 (70%) cases. Most frequently used conditioning
regimens were BEAM (BeEAM): carmustine (or bendamustine),
etoposide, cytarabine, melphalan (n =39, 59%) or 12 Gy TBIbased
protocols (n =17, 26%).
The analysis of prognostic factors was focused on conditioning
regimens, pretransplant rituximab resistance, history of early
(less than 24 months) treatment failure (ETF) and Deauville
scoring of 3 in pretransplant PETCT (data available for 56
patients).
Results: Median number of transplanted CD34+cells was 3.7 10
6
/
kg (0.848.3). All patients engrafted. The median time to neutrophil
recovery was 11 days (916) while platelet count >20 10
9
/L was
reported after a median of 11 days (023).
Median followup was 48 months (1235). 20 patients (30%) relapsed
during the followup, 6 patients (9%) died. Only one patient died
without disease progression in day +333 due to pulmonary causes.
Median overall survival (OS) was not reached, whereas median
progressionfree survival (PFS) was 115 months. Probabilities of OS
and PFS at 5 years were 85% and 55%, respectively. One case of
secondary malignancy was reported (Hodgkin lymphoma 10 years
after autoHSCT).
In a univariate analysis the probability of OS at 5 years was
decreased for patients with prior ETF (81.8% vs. 100%, p =0.04) and
Deauville 3 (83.3% % vs 97.7%, p =0.02), whereas no adverse
factors for PFS were found.
Conclusion: Results of our analysis show that autoHSCT is a safe
and valid option for r/r FL patients with low transplantrelated
mortality. Longterms PFS suggests that autoHSCT may have
curative potential in a subset of patients with FL. Prior ETF and
Deauville score of 3 in PETCT before transplantation are adverse
factors for OS. In these cases, alternative treatment options should
be considered.
SUPPLEMENT ABSTRACTS
-
405
Keywords: Stem Cell Transplant
No conflicts of interests pertinent to the abstract.
312 |A NONINTERVENTIONAL STUDY OF OBINUTUZUMAB
IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED
FOLLICULAR LYMPHOMA (URBAN): IMPACT OF COVID19
PANDEMIC ON ENROLLMENT AND SAFETY
A. Pinto
1
, P. L. Zinzani
2
, L. Arcaini
3
, G. Gritti
4
, C. Patti
5
, E. Pennese
6
,
S. De Lorenzo
7
, C. Piparo
8
, E. Guardalben
9
, M. Ladetto
10
1
Istituto Nazionale Tumori, Fondazione ‘G. Pascale', IRCCS, Ematologia
Oncologica, Naples, Italy,
2
Università di Bologna, Istituto di Ematologia
“Seràgnoli”, Bologna, Italy,
3
Fondazione IRCCS Policlinico San Matteo,
Divisione di Ematologia, Pavia, Italy,
4
Ospedale Papa Giovanni XXIII,
Ematologia, Bergamo, Italy,
5
Azienda Ospedali Riuniti Villa SofiaCervello,
Oncoematologia, Palermo, Italy,
6
Ospedale Santo Spirito, Dipartimento di
Oncologia ed Ematologia, Pescara, Italy,
7
Azienda Ospedaliera Rilievo
Nazionale (A.O.R.N.) S. Giuseppe Moscati, Ematologia, Avellino, Italy,
8
Roche Spa, Clinical Operations, Monza, Italy,
9
Roche Spa, Medical
Affairs, Monza, Italy,
10
Azienda Ospedaliera Santi Antonio e Biagio e
Cesare Arrigo, Ematologia, Alessandria, Italy
Background. The introduction of new agents has improved the
prognosis of follicular lymphoma (FL). Unfortunately, COVID19
pandemic may have affected disease management.
Objective. The noninterventional, retrospective/prospective UR-
BAN study is aimed to evaluate effectiveness and safety of
Obinutuzumabbased treatment in reallife practice of patients with
untreated advanced FL with FLIPI2. The study is ongoing in 46 sites
in Italy. The objective of this interim analysis is to evaluate patient
characteristics, potential changes in the management due to COVID
19 pandemic, preliminary efficacy at the end of induction (EOI) and
safety data collected about 1 year after the first patient enrolled.
Methods. Participants should have received at least 2 cycles of
Obinutuzumabchemotherapy induction before the enrollment
(retrospective part of the study). The study, launched in Sep2019
includes 68 induction courses, 2year maintenance with Obinutu-
zumab monotherapy, and 1year followup period after the last
Obinutuzumab administration. Two time periods have been analyzed:
406
-
SUPPLEMENT ABSTRACTS
preCOVID19 phase (until 24Feb2020) and COVID19 phase (25
Feb2020 to 09Oct2020; clinical cutoff date).
Results. Overall, 266 patients (median age 61 years, 56% females)
were enrolled: 186 patients began the treatment preCOVID19
(preC group) and 80 patients during COVID19 (C group).
Among the trends, not statistically significant, from this analysis,
more patients in the C group vs preC group initiated treatment with
Bsymptoms (26.2% vs 19.4%; p =0.357) and more advanced (IIIIV)
disease stage (95% vs 90.9%; p =0.605).
Fewer patients in the C group than in the preC one (41.2% vs
48.9%; p =0.309) received bendamustine, resulting in reversed rates
for CHOP adoption (55% in C and 44.1% in preC; p =0.133).
As to safety, in the retrospective part of the study neutropenia
occurred in 22.9% of patients, infusionrelated reactions in 12.8%,
thrombocytopenia in 9.4%, and infections in 7.5%. In the prospective
part they were 17.7%, 0.8%, 2.3%, and 8.6%, respectively. One pa-
tient had a grade 3 COVID19 infection, which required treatment
withdrawal. No data is yet mature about possible changes in main-
tenance strategies due to COVID19.
Preliminary efficacy data, available for 164 patients at EOI, show
that 134 patients (81.7%) achieved a PETCT CR (confirmed by BM
evaluation for 46/73 patients positive at baseline), and 25 (15.2%) a
PR.
Conclusions. The interim analysis of the URBAN study shows that
Obinutuzumabbased treatment is associated with a good safety and
efficacy profile. Furthermore, the observed trends might suggest that
during pandemic the adoption of a watchandwait strategy is wider
and the use of bendamustine reduced, possibly due to concerns on
more severe and prolonged induced lymphodepletion; therefore
COVID19 might have influenced the clinical approach to the treat-
ment of FL patients.
The research was funded by: Roche Spa, Monza, Italy
Keywords: Indolent nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
C. Piparo
Employment or leadership position: Roche employee
E. Guardalben
Employment or leadership position: Roche employee
313 |CLINICAL CHARACTERISTICS AND OUTCOMES OF
WALDENSTRÖM MACROGLOBULINEMIA PATIENTS, TREATED
AND FOLLOWED IN A PUBLIC BRAZILIAN CENTER.
G. B. Duffles Amarante
1
, R. S. Szor
1
, A. Duran
1
, L. B. d. O. Alves
1
,
G. Martinez
1
, J. Pereira
2
, V. G. Rocha
1
1
Serviço de Hematologia, Hemoterapia e Terapia celular, Hospital das
Clínicas, Faculdade de medicina da Universidade de São Paulo (USP),
Hematology, São Paulo, Brazil,
2
Laboratory of medical investigation in
pathogenesis and directed therapy in oncoimmunohematology,
Faculdade de medicina da Universidade de São Paulo (USP), Hematology,
São Paulo, Brazil
Waldenström macroglobulinemia (WM) is a rare disease, account-
ing for less than 2% of nonHodgkin`s lymphoma. Current data on
the clinical and epidemiological characteristics of the disease are
widely from European and American centers. Data on Brazilian
WM patients are scarce in the literature, represented only by case
reports.
This study aimed to retrospectively assess clinical features,
treatment options and outcomes of patients diagnosed with WM
from 1999 to 2017 at a single university center in Sao Paulo,
Brazil.
Fifty patients met the eligibility criteria, 31 (62%) males with
median age at diagnosis of 63.5 years (range 4284). The median
(IQR) values of blood tests at presentation were: hemoglobin 9.1g/dl
(7.911), platelet 178.000/mm
3
(112240), β
2
M 3.6g/dl (2.65.0),
calcium 9.1mg/dl (8.89.6), IgM 3495mg/dl (3689759). Median time
from diagnosis to start of treatment was 41 days (minmax, 0966).
IPSSWMR was very low and low risk in 38%, while 42% of cases
were high or very high risk. All but 3 patients (watch and wait) were
treated. The following indications for treatment were available in 38
patients: anemia (71%), thrombocytopenia (26%), B symptoms (47%),
hyperviscosity syndrome (18%), progressive adenopathy/bulky dis-
ease (8%), symptomatic neuropathy (8%) and hemolytic anemia (8%).
The main chemotherapy protocols for firstline therapy were: CVP
(37.5%), chlorambucil (20.8%) and FC (10.4%). Overall response rate
(ORR) was 45.7%, mainly partial remission (PR) (37.1%). Stable dis-
ease occurred in 28.5% and progressive disease in 25.7% of cases.
Thirtyone patients (62%) received secondline therapy. The most
prescribed protocols were CVP (n =10), CHOP (n =5), Fludarabine
(n =4), chlorambucil (n =4) and FC (n =3). PR was the commonest
response (45%). The median followup time was 4.0 years (010, IQR).
Estimated 4year OS was 63% (CI 95%, 4676), and 4year PFS was
35% (CI 95%, 2149).
Our study reflects a realworld experience of a rare disease in a
public health university center in a middleincome country, with
resource constrained limitations. Our study has limitations, mainly
related to its retrospective design. Moreover, genotype test is not
reimbursed and there is no approval for Rituximab, Bendamustine or
Bruton tyrosine kinase inhibitors in Brazil's public health system for
WM. Even with those limitations, our results seem to be comparable
with previous reported data of the DRC protocol, albeit with lower
ORR. Our patients were younger, with lower hemoglobin levels and
with more B symptoms than other studies. In addition, difficult access
to health care assistance delays diagnosis. Efforts should be made to
perform genotype tests and make available specific treatment for
MW. Medical education, establishment of a reference center and a
national registry may improve knowledge of MW and outcomes of
patients in Brazil and other countries.
Keywords: Indolent nonHodgkin lymphoma, Multiple Myeloma
No conflicts of interests pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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407
314 |ENDPOINTS IN MARGINAL ZONE LYMPHOMAS: A
SYSTEMATIC REVIEW REVEALS WIDE HETEROGENEITY ACROSS
TRIALS AND CALLS FOR STANDARDIZATION.
C. Bommier
1
, M. Ruggiu
2
, A. Monegier
3
, E. Zucca
4
, C. Thieblemont
5
, J.
Lambert
6
1
Hôpital Saint Louis, Oncohematology department, U1153 Inserm
ECSTRRA Team, Paris, France,
2
Hôpital Saint Louis, Hematopoietic stem
cell transplant, Paris, France,
3
Hôpital Saint Louis, Statistics and Bioin-
formatics, Paris, France,
4
Ospedale Regionale di Bellinzona e Valli, IELSG,
Bellinzona, Switzerland,
5
Hôpital Saint Louis, Hematooncology, Paris,
France,
6
Hôpital Saint Louis, Statistics and Bioinformatics, Inserm U1153
ECSTRRA Team, Paris, France
*the two last authors contributed equally to this work.
Introduction:Marginal zone lymphoma (MZL) is a heterogeneous
disease, which indolent course requires long and costly trials to
evaluate novel therapeutics. There is a need to find more specific and
shorter endpoints. Our aim was to carry out an inventory of the
endpoints used in trials involving at least 1 MZL patient.
Methods:We performed a systematic review of the endpoints used in
published and registered trials in marginal zone lymphoma. We
searched via PubMed, The Cochrane Library, clinicaltrials.gov and
clinicaltrialsregister.eu for published and registered “clinical trials”
using the keyword “marginal zone lymphoma”. We included studies
on human adult patients (18 years or older) treated for a MZL; we
excluded studies focusing on pediatric populations, cutaneous mar-
ginal zone lymphoma and on use of allogenic stem cell transplant.
Inclusions were doublechecked and data extraction was performed
by two blinded reviewers.
Results:1192 references were identified by the initial screening.
Among the 309 included references (111 published, 198 registered),
214 (69%) were phase II, 65 (21%) phase III and 30 (10%) phase I/II
trials. The majority of them were openlabel (n =295, 95%) non
randomized (n =256, 83%) trials, concerned all subtypes of MZLs at
once (n =239, 77%), and were often merged with nonMZL patients
(n =231, 75%). Overall/complete response rate (ORR/CRR) was the
most used primary endpoint (n =208, 67%), followed by progression
free survival (PFS, n =49, 16%). The most frequent secondary end-
points were overall survival (OS, n =153, 50%), PFS (n =142, 46%) and
408
-
SUPPLEMENT ABSTRACTS
ORR/CRR (n =116, 38%). Distribution of endpoints was similar when
considering trials with only MZL patients. ORR/CRR was significantly
more used as primary endpoint in phase 2 trials (70.5% vs 19.4%),
while PFS was more used in phase 3 trials (58.1% vs 10.1%, p <0.001).
Choice of primary endpoint was not influenced by neither family of
treatment (targeted vs no targeted therapy, p =0.92) nor funder type
(p =0.46). Same endpoints were defined differently across published
trials. ORR was reported either as best response (76%) or response at
a fixed time point (24%); death was not mentioned as a component of
PFS in 13/97 (13%) trials; 9 different definitions were used for Event
free survival and as many for Time to failure.
Conclusion: Trials involving MZL patients showed marked heteroge-
neity both in the choice and definitions of primary and secondary
endpoints. Standardization is needed among international in-
vestigators in order to allow comparability between trials.
Primary and secondary endpoints used in trials involving MZL pa-
tients, according to their study design. (up) involving at least 1 MZL
patient; (bottom) including only MZL patients. MZL: marginal zone
lymphoma. Phase III trials are colored in green, phase II trials in yellow
and phase I/II trials in pink.
The research was funded by: First author of this abstract is funded by
a public grant from Agence Régionale de Santé ÎledeFrance as part
of a PhD graduation.
Keywords: Indolent nonHodgkin lymphoma, Therapeutics and Clin-
ical Trials in Lymphoma Other
No conflicts of interests pertinent to the abstract.
315 |CLINICAL OUTCOMES IN PATIENTS RELAPSED/
REFRACTORY AFTER 2 PRIOR LINES OF THERAPY FOR
FOLLICULAR LYMPHOMA: A SYSTEMATIC LITERATURE REVIEW
AND METAANALYSIS
S. Kanters
1
, B. Kahl
2
, A. Wiesinger
3
, B. Gurung
4
, E. H. Limbrick
Oldfield
1
, A. Sudhindra
3
, J. Thornton Snider
3
, A. R. Patel
3
1
RainCity Analytics, Vancouver, Canada,
2
Washington University School
of Medicine in St. Louis, 2. Oncology Division, Department of Medicine, St
Louis, USA,
3
Kite, A Gilead Company, Santa Monica, USA,
4
Health
Economics & Outcomes Research, IQVIA, London, UK
Introduction: Patients with follicular lymphoma (FL) can have high
response rates to early lines of treatment. However, among FL pa-
tients relapsed/refractory (r/r) after 2 prior lines of therapies (LOT),
remission tends to be shorter and there is limited treatment guid-
ance. This study sought to evaluate the clinical outcomes for r/r FL
after 2 prior LOT using available treatment options.
Methods: Electronic databases were searched on 2
nd
June 2020.
Eligible studies were comparative or noncomparative interventional
or observational studies of systemic therapies among adults with FL r/
r after 2 prior LOT. Prior LOT must have included antiCD20
monoclonal antibodies and alkylating agents, in combination or
separately. Overall response rate (ORR) and complete response (CR)
were analyzed using inversevariance weighting with FreemanTukey
doublearcsine transformations. KaplanMeier (KM) analysis for
progressionfree survival (PFS) and overall survival (OS) were con-
ducted using digitized curves and the Guyot algorithm. Survival ana-
lyses were stratified by 2 prior LOT and 3 prior LOT groups and
were restricted to the observational cohorts as a sensitivity analysis.
Results: The metaanalysis included 12 studies published from 2014
2020. Sample size for response outcomes was 340, for survival
outcomes with 2 prior LOT was 1024 and for 3 prior LOT was
502. The estimated ORR in the 2 prior LOT group was 56.0% (95%
confidence interval [CI]: 47.2 64.5) and proportion of patients with
CR was 12.2% (95% CI: 8.0 17.3). The median OS was 54.4 months
(95% CI: 45.8 76.0) and median PFS was 10.3 months (95% CI: 9.3
11.1). The 24month OS decreased from 66% in the 2 prior LOT
group to 60% in the 3 prior LOT group (Table 1), with a similar
trend in PFS at 24month (28% vs 24%).
Conclusions: This study found that few r/r FL patients with 2 prior
LOT achieve CR, and despite some benefit, approximately 1/3 of
patients die within 24 months. The shorter median PFS with
increasing prior LOT suggest treatment durability is suboptimal in
TABLE 1Key outcomes
SUPPLEMENT ABSTRACTS
-
409
later LOT. These findings indicate that patients are underserved by
current treatments, demonstrating a need for new treatments that
can achieve high rates of durable response in this disease.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: This project was funded by Kite, a
Gilead company.
Keywords: Indolent nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
S. Kanters
Employment or leadership position: RainCity Analytics
Research funding: RainCity Analytics has received funds from for
profit healthcare companies for research
B. Kahl
Consultant or advisory role: Abbvie, Acerta, AstraZeneca, Celege,
Kite, Genentech, Pharmacyclics, MEI
Research funding: Genentech, Celgene, Acerta, AstraZeneca
A. Wiesinger
Employment or leadership position: Kite, A Gilead Company
Stock ownership: Kite, A Gilead Company
B. Gurung
Employment or leadership position: IQVIA Ltd
Research funding: IQVIA Ltd
E. H LimbrickOldfield
Employment or leadership position: RainCity Analytics
A. Sudhindra
Employment or leadership position: Atara Biotherapeutics, Kite
Pharma
Stock ownership: Atara Biotherapeutics, Gilead
J. Thornton Snider
Employment or leadership position: Kite, A Gilead Company
Stock ownership: Gilead Sciences
Research funding: Previously employed at PrecisionHEOR, which
receives research funding from life sciences companies.
A. R Patel
Employment or leadership position: Kite, A Gilead Company
Stock ownership: Kite, A Gilead Company
MANTLE CELL LYMPHOMA
316 |THE CONTRIBUTION OF MONOCYTETOPLATELET
RATIO TO PREDICT OVERALL SURVIVAL IN MANTLE CELL
LYMPHOMA: A SINGLECENTER SURVEY
F. Lorenzano
1
, G. Santuccio
1
, L. Caruso
2
, A. Chiarenza
2
, A. Figuera
2
,
G. Motta
2
, F. Di Raimondo
1
, A. Romano
1
1
University of Catania, Dipartimento di Chirurgia e Specialità Medico
Chirurgiche, Catania, Italy,
2
AOU Policlinico Rodolico San Marco, Divi-
sione di Ematologia, Catania, Italy
In mantle cell lymphoma (MCL) the activity and number of tumour
immune microenvironment (TIME) cells can be defined by some im-
mune dysregulation and chronic inflammation markers, such as
neutrophiltolymphocyte ratio (NLR) and monocytetoplatelet ratio
(MPR). In lack of studies about the contribution of NLR and MPR in
MCLTIME lacking, we investigated their prognostic value in a
retrospective singlecenter series.
Methods: We reviewed the clinical files of 122 MCL patients, with a
confirmed histological diagnosis of MCL who accessed our centre
from 21/06/2000 to 28/05/2020. Due to the lack of complete data
regarding some of these patients, the statistical analyses were
conducted on 108 of them. We analysed the correlation between
immune dysregulation markers and overall survival (OS) at 60
months.
Results: The median age at diagnosis was 69 years (ranging between
36 and 85 years); 81 of the patients (74.31%) were male. A complete
blood count was performed routinely for each of these patients to
white blood cell count with differential (median WBC 8580/µL
ranging from 2530/µL to 217790/µL; median ANC 3960/µL ranging
from 520/µL to 14220/µL; median ALC 2000/µL ranging from 60/µL
to 197750/µL; median AMC 560/µL ranging from 20/µL to 11310/
µL), platelet count (median PLT 170500/µL ranging from 19000/µL to
412000/µL), haemoglobin levels (median Hb 12.35 g/dL ranging from
7 g/dL to 16.3 g/dL) and various immune dysregulation and chronic
inflammation markers (such as NPR, with a median of 24.6 and
ranging from 4.19 to 277.33; NLR, with a median of 1.7 and ranging
from 0.03 to 111.6; LMR, with a median of 4.17 and ranging from
0.17 to 450.14; PLR, with a median of 0.0893 and ranging from
0.0009 to 1.54).
In the whole cohort of patients, univariate survival analysis showed a
significative prolonged OS at 60 months in patients carrying baseline
MPR 7.5 (median OS: 35.3, HR =1.82; p =0.03; p value: 0.03). In
patients with age 70, only Ki67 25% was correlated with OS
(HR =2.39; p =0.008). In patients with age <70, several factors were
significative in univariate analysis, including: presence of B symptoms
(HR =3; p =0.001), PSECOG 3 (HR =3.13; p =0.008), male gender
(HR =3.39; p =0.03), Ki6725% (HR =2.39; p =0.02), MPR 7.5
(HR =2.44; p =0.03) and NLR 6 (HR =2.63; p =0.01). In multivariate
analysis, presence of B symptoms, male gender, MPR 7.5 and NLR 6
were independent predictors of OS at 60 months.
Conclusions: Between the immune dysregulation markers analysed,
MPR and NLR can be considered valid prognostic factors in MCL
setting. NLR, according to our results, is a valuable marker for less
than 70 years old patients, while MPR resulted to be valid in the
whole cohort of patients. Larger and functional studies of mono-
cyte behavior in MCL are required to explore the contribution of
MPR in predicting clinical outcome in this setting.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
410
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SUPPLEMENT ABSTRACTS
317 |REAL WORLD OUTCOME IN MANTLE CELL LYMPHOMA:
A FRENCH RETROSPECTIVE STUDY IN ELDERLY PATIENTS
BETWEEN 2005 AND 2018
B. Branco
1
, P. Bories
1
, L. Ysebaert
1
, C. Laurent
2
, B. Cabarrou
3
, T.
Botin
4
, Y. Leveneur
5
, L. Ghenim
6
, M.H. Gaspard
7
, N. Hess
8
, W.
Vaillant
9
, M. Carreiro
10
, L. Oberic
1
1
IUCTOncopole, Haematology, Toulouse, France,
2
IUCTOncopole, Pa-
thology, Toulouse, France,
3
IUCTOncopole, Biostatistics, Toulouse,
France,
4
Centre Hospitalier Intercommunal CastresMazamet, Haematol-
ogy, Castres, France,
5
Centre Hospitalier de Bigorre, Internal Medicine,
Tarbes, France,
6
Centre Hospitalier de Rodez, Oncology, Rodez, France,
7
Clinique Claude Bernard, Oncology, Albi, France,
8
Clinique du Pont de
Chaume, Oncology, Montauban, France,
9
Centre Hospitalier de Auch,
Haematology, Auch, France,
10
Centre Hospitalier de Montauban,
Oncology, Montauban, France
Introduction: First line treatment of patients with mantle cell
lymphoma (MCL) otherwise ineligible to stem cell transplant is
not well standardized. While being predominantly diagnosed in
elderly people, scarse data is available in this population outside
trials. We aimed to describe clinical management in a large unse-
lected cohort of MCL patients, and evaluate their outcomes in a real
world setting.
Methods: We identified patients aged 65 years and diagnosed with
MCL, between 20052018 in a 2.8 M inhabitants region (accounting
for 4.25% of France population). Demographics, baseline biological
and clinical features were analyzed using descriptive statistics.
Progressionfree (PFS) and overall (OS) survival were estimated using
KaplanMeier method.
Results: We identified 260 patients with a median age at diagnosis of
75 years (range 6590), with 71 being 80 years old. 83% of patients
had ECOG 01, while only 14% having B symptoms. Median CIRSG
comorbidities score was 5 (range 014). 91% patients had stage IIIIV
disease, blastoid variant represented 14% of all diagnoses. MIPI score
was available in 199 patients: high in 66%, intermediate in 29% and
low in 5%.
250 patients received 1 treatment immediately after diagnosis
(n =211) or after a period of watch and wait (n =39). Deferred
treatment had no impact neither on OS or PFS. Patients received
anthracyclines (51%), chlorambucil (24%), bendamustine (13.3%) or
cytarabine (5.2%) based regimens, the majority in combination with
rituximab (n =241).
After a median followup of 56.6 months, median OS was 61.3
months (Fig 1A) and median PFS was 23.6 months for the treated
patients population. The 2and 5y OS rates were 77.2% and 54.0%
respectively, with 2and 5y PFS rates of 47.4% and 21.4%,
respectively.
Type of firstline chemotherapy was not associated with OS nor PFS,
except for patients receiving chlorambucil whom had worse OS than
those treated by anthracyclines (HR 1.7 ; 95%CI =[1.1;2.6]).There
was no improvement in survival curves based on year of first therapy,
20052011 versus 20122018 (Fig 1B).
In multivariable analysis, only CIRSG score, medullar involvement
and MIPI score were associated with worse OS.
POD24 (progression of disease within 24 months of treatment) had
an impact on survival (HR 3.5 ; 95%CI =[2.0;6.1] ; p <0.0001),
SUPPLEMENT ABSTRACTS
-
411
median OS was 50.1 versus 113.7 months for POD24 versus no
POD24 patients. A total of 66 patients received ibrutinib at any line
of relapse, with a median OS and PFS of 16.6 and 8.2 months
respectively, after a median followup of 16.4 months. Upon pro-
gression while on ibrutinib, median OS was only 6.3 months.
Conclusions: This large retrospective study dedicated to elderly pa-
tients with newly diagnosed MCL confirms previously described
prognostic factors. We observe no improvement in survival since
2005 despite availability of new therapeutic options (rituximab
maintenance, bendamustine, ibrutinib). Continuous evaluation of
novel strategies and their incorporation in first line treatment to
improve outcomes are needed in this frail population.
Keywords: Indolent nonHodgkin lymphoma, Lymphoid Cancers
Other
No conflicts of interests pertinent to the abstract.
318 |MANTLE CELL LYMPHOMA, A SINGLE CENTER
EXPERIENCE
A. Roumelioti
1
, C. Giatra
1
, M. Dellatola
1
, E.K. Dimitraki
1
, M.
Bouzani
1
, G. Kanellis
2
, D. Ikonopoulou
1
, K. Kaouranis
1
, N. ElGkotmi
1
,
A. Loutsidi
1
, P. Kosmas
1
, I. Darmani
1
, K. Souravla
1
, V. Babali
1
, D.
Gardeli
1
, L. Ligdi
1
, E. Andreou
1
, G. Tounta
1
, Z. Mellios
1
, F. Kar-
aolidou
1
, I. Tsonis
1
, T. Tzenou
1
, S. Gigantes
1
, I. Baltadakis
1
, D. Kar-
akasis
1
, K. Sakellariou
1
, D. Rontogianni
3
, M. Bakiri
1
, T. Karmiris
1
1
Evaggelismos General Hospital, Hematology & Lymphoma Department,
BMTU, Athens, Greece,
2
Evaggelismos General Hospital, Department of
Hematopathology, Athens, Greece,
3
Evaggelismos General Hospital,
Department of Pathology, Athens, Greece
Introduction: Mantle Cell Lymphoma (MCL) is an indolent Bcell
non Hodgkin Lymphoma (NHL) with a worse outcome compared
to other low grade NHL. The prognosis of the disease is dictated by
various biologic and clinical factors. Although MCL is chemo-
sensitive in newly diagnosed patients, soon it relapses. A significant
improvement of its outcome has been achieved by the administra-
tion of Rituximab (R) based regimens and the intensification of first
line treatment by high dose Cytarabine and autologous stem cell
transplantation.
Methods: To reveal the experience of our Centre on the diagnosis,
treatment and outcome of this difficult to treat lymphoma, we
collected data from 51 consecutive patients, diagnosed at our
department between 1999 and 2020.
Results: Thirty nine (39) men and 12 women with median age 68
years (range 3388) were diagnosed with MCL. All but one had
typical histology. One patient manifested the blastoid variant. Ki67
was available for 39 biopsy: In 57% specimens Ki67 was >30% and in
43% Ki67 was 30%. In 84% of cases the performance status at
diagnosis was good (PS 01) and only 16% showed PS 24. The ma-
jority of patients (90%) had advanced stage disease (IIIIV). High MIPI
score was observed in 59%, intermediate in 18% and low in 22%.
Elevated lactate dehydrogenase was observed in 58% of cases.
Nineteen patients received R Cyclophosphamide, Hydroxydaunor-
ubicin, Oncovin, Prednisone (RCHOP), 11 an intensified regimen, 14
patients R Bendamustin, 5 patients R Chlorambucil and 2 subjects
had no treatment. Response to treatment showed as follow: Com-
plete Response (CR) 52%, Partial Response (PR) 36%, Stable disease
(SD) 2% and Progressive Disease (PD) 10%. Among patients who
received an intensified treatment, 9 underwent an autologous
transplantation. Twenty two patients with responsive disease bene-
ficed of R maintenance. Over a median follow up of 62.8 months
(range 0.3 262), the median overall survival (OS) was 165 months
(range 0.3 262). Twenty three out of 44 (52%) patients with
responsive disease, relapsed. The median progression free survival
(PFS) was 59 months (range 6 140). Sixteen out of 23 (69%) patients
achieved a 2nd response. The treatments administered were: R
CHOP (6 patients), RBendamustin (6 patients), platinum based
regimens (3 patients), Ibrutinib (5 patients), corticosteroids (2 pa-
tients), R Chlorambucil (1 patient). The median PFS and OS after the
1st relapse were 26.4 months (range 6.9 165) and 27 months (range
0.2 233) respectively. Response to 1st line treatment (p 0.0001),
lower MIPI score (p 0.001) and intensified regimen (p 0.0004) were
correlated with a better survival.
Conclusions: Increasing the percentage of 1st complete response by
intensifying the 1st line treatment could improve the survival of
patients with MCL.
Keywords: Indolent nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
319 |IBRUTINIB IN PATIENTS WITH RELAPSED/REFRACTORY
MANTLE CELL LYMPHOMA: REAL LIFE DATA FROM THE 'RETE
EMATOLOGICA DEL LAZIO PER I LINFOMI' (RELLi)
S. Mariani
1
, S. Pelliccia
1
, M. P. Bianchi
1
, A. Di Rocco
2
, L. Petrucci
2
,
E. Maiolo
3
, R. Battistini
4
, F. Fanelli
4
, G. Tomei
5
, F. Palombi
6
, E. Papa
6
,
L. Pupo
7
, A. Andriani
5
, S. Hoaus
3
, M. Cantonetti
7
, C. Tesei
1
, A. Tafuri
1
1
A.O.U. Sant'Andrea, Sapienza University of Rome, Dipartimento di
Medicina Clinica e Molecolare, Rome, Italy,
2
Hematology, Sapienza
University of Rome, Department of Translational and Precision Medicine,
Rome, Italy,
3
Università Cattolica S. Cuore, Department of Hematology,
Rome, Italy,
4
AO San CamilloForlanini, Haematology and Haematopoietic
Stem Cells Transplant Unit, Rome, Italy,
5
Fabrizio Spaziani Hospital, He-
matology, Frosinone, Italy,
6
IRCCS Regina Elena National Cancer Institute,
Hematology and Stem Cell Transplant Unit, Rome, Italy,
7
Haematology
Division, University of Tor Vergata, Department of Biomedicine and Pre-
vention, Rome, Italy
Introduction: Treatment of relapse/refractory (R/R) mantle cell
lymphoma (MCL) patients lacks a gold standard therapy. Ibrutinib is a
Bruton Tyrosine Kinase (BTK) inhibitor approved in this setting.
412
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SUPPLEMENT ABSTRACTS
Results obtained from the registration studies (PCYC1104,
MCL2001, MCL3001) reported 68%, 63% and 72% of overall
response rate (ORR), and 1.9, 10.5 and 14.6 months of median
progressionfree survival (PFS), respectively. However, a less favor-
able outcome is reported in terms of ORR in real life studies: ORR
ranging from 36,4 % to 65% and median PFS from 12,9 to 15 months
(Broccoli A et al, 2018, Epperla N et al, 2017). Therefore, we aimed to
retrospectively evaluate R/R MCL patients treated with Ibrutinib in
RELLi network.
Methods: Patients included in this study were diagnosed with R/R
MCL between January 2004 and April 2020 in several institutions
belonging to the RELLi. Clinical characteristics, treatments and out-
comes were analyzed.
Results: Thirtyfour patients (M:21, F:13) with a median age of 67,5
years (range 4284) were included. At diagnosis, 82.3% of patients
presented at Ann Arbor stage III/IV and 76.4% showed a classic
form (11.8% for both blastoid and pleomorphic variant). Patients
with high MIPI score were 70.6% and those with Ki67 >30% were
85%. Patients were treated with different frontline therapies:
intensive chemotherapy followed by ASCT, RCHOP (or R CHOP
like) and Bendamustinebased regimens (RBAC/RBenda) in 29.4%,
26.4% and 32.3%, respectively. Patients analyzed were in second,
third and fourth line of treatment, 61%, 23% and 16% respectively.
After Ibrutinib treatment, patients achieved complete remission
(CR), partial response (PR) and progressive disease (PD) in 58%,
18% and 24%, respectively. With respect to age, 41% were <65
years, among these 64% underwent ASCT as frontline treatment.
Older patients (>65 years) were 59%, of whom 45% underwent
treatment based on RBAC/Benda and 55% based on RCHOP like.
Notably, 38% of patients were >70 years and 14% of them (5
cases) were >80 years. The toxicities were: G1 hyperamylasemia
(one case), G2 neutropenia (two cases) and G1 thrombocytopenia
(one case). One acute myocardial infarction was reported in a pa-
tient in CR requiring Ibrutinib discontinuation. The median overall
survival (OS) was 50% after a median followup of 141 months and
the median PFS was 21 months. The median OS for CR was not
reached, and for PR and PD patients was 11 and 23 months,
respectively (p 0.023).
Conclusions: Our study confirms the efficacy of Ibrutinib in pa-
tients with R/R MCL, with a good safety profile. However, dis-
crepancies emerged with respect to reallife studies (ORR of 76%
vs. 36,465% and median PFS of 21 months vs. 12.915 months),
confirming in our series data from registration studies. Moreover,
the toxicity data analysis showed no need of dose reduction ac-
cording to age, encouraging this approach also in the elderly R/R
MCL patients.
Keywords: Aggressive Bcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
A. Tafuri
Research funding: Roche, Novartis, Celgene, AbbVie
AGGRESSIVE NHL
320 |CHIDAMIDE WITH PEL REGIMEN (PREDNISONE,
ETOPOSIDE, LENALIDOMIDE) FOR ELDER OR FRAIL PATIENTS
WITH RELAPSED/REFRACTORY DIFFUSE LARGE BCELL
LYMPHOMA
Y. Wang
1
, H. Xue
1
1
The Affiliated Hospital of Qingdao University, Hematology, Qingdao,
China
Background: Diffuse large Bcell lymphoma (DLBCL) is the most
common form of nonHodgkin lymphoma and is increasing in inci-
dence, particularly for elderly people. Treatment for relapsed/re-
fractory DLBCL is evolving rapidly due to emergence of novel drugs,
and HDACi is an important one of these drugs.
Methods: In this study we report the experiences with chidamide
containing regimen CPEL(chidamide, prednisone, etoposide and lena-
lidomide)with or without rituximab(R)in refractory or relapsed DLBCL
(R/R DLBCL) who were not eligible for intensive chemotherapy and
autologous stem cell transplantation(ASCT) due to physical condition
of their age, comorbidities or unwillingness to accept ASCT. This is an
observational retrospective analysis. We retrospectively analyzed the
characteristics of this cohort of patients and their response to the
novel regimen of chidamide in combination with PET regimen (pred-
nisone, etoposide and lenalidomide).
Results: Between June 2018 and June 2020, a total of 34 patients with
R/R DLBCL were treated with CPEL+/R at least 2 cycles in the Affil-
iated Hospital of Qingdao University. The interim ORR was 76.5%
(44.1% PR, 32.4%CR), and the ultimate ORR was 50% (20.6% PR, 29.4%
CR), after the median followup of 20.9 ±6.2 months (95% confidence
interval [CI]8.733.1), the median progressionfree survival(PFS) was
13.4 ±3.6 months (95%CI 6.220.6) and the median overall survival
(OS) was19.3 ±3.9 months (95%CI 11.727.0). The 1year expected
PFS rate was 50%, and the 1year expected OS rate was 68.5%. The
most common grade 3/4 adverse events was hematology,11(32.4%)
patients had neutropenia, 4 patients (11.8%) suffered anemia and 2
patients (5.9%) had thrombocytopenia. 8 patients suffered grade 3/4
nonhematologic adverse events, among which one patient had grade 4
PE (pulmonary embolism) and other grade 3/4 adverse events were
fatigue, infection, thrombogenesis, anorexia and hyponatremia.
Conclusions: ChidamidePET regimen is an efficient and tolerable
regimen for older R/R DLBCL patients unfit for intensive
chemotherapy.
The research was funded by: This work was supported by the Beijing
CSCO Clinical Oncology Research Foundation Programs
(Y247HR2018270).
Keywords: Molecular Targeted Therapies, Combination Therapies,
Immunotherapy
No conflicts of interests pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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413
321 |TEMOZOLOMIDE, ETOPOSIDE, DOXIL,
DEXAMETHASONE, IBRUTINIB AND RITUXIMAB FOR THE
TREATMENT OF RELAPSED OR REFRACTORY CENTRAL
NERVOUS SYSTEM LYMPHOMA IN CLINICAL PRACTICE
Author(s): U. Ringeleviciute
1
, S. Cernauskiene
1
, A. Zucenka
1
,
R. Pileckyte
1
, L. Griskevicius
1
1
Vilnius University Hospital Santaros Klinikos, Hematology, Oncology and
Trasfusion Medicine Center, Vilnius, Lithuania
Introduction. Introduced in 2015, DATEDDIR (dose adjusted
temozolomide, etoposide, liposomal doxorubicin, dexamethasone,
ibrutinib and rituximab) regimen has showed acceptable toxicity and
promising survival rates not only in primary CNSL but also in sec-
ondary CNSL which is generally associated with poor prognosis.
Methods. We retrospectively collected data on CNSL patients
treated with TEDDIR (Inhibition of B Cell Receptor Signaling by Ibru-
tinib in Primary CNS Lymphoma, June 12, 2017, https://www.cell.com/
cancercell/pdfExtended/S15356108(17)301678) in Vilnius Uni-
versity Hospital Santaros Klinikos from 2018 to 2020. Response was
evaluated by gadoliniumenhanced MRI according to the Interna-
tional PCNSL workshop response criteria. The end points were
overall survival (OS), progression free survival (PFS) and grade 35
toxicity. The toxicity was evaluated according to Common Termi-
nology Criteria for Adverse Events v5.0.
Results. 13 patients (9 male) were included. The median age was 55
years (2870) and median performance score was 2 (04). 12 patients
had relapsed of refractory R/R CNSL and one patient was intolerant to
highdose methotrexate. Highgrade Bcell histology was verified in all
cases. 7/13 (54 %) cases had primary CNSL. 5 of these patients had had
autologous stem cell transplantation (autoSCT) prior to relapse. Of 6
(46%) secondary CNSL patients, highdose methotrexate CNS pro-
phylaxis had previously been administered in 5 (83 %). In total, 43
cycles of TEDDIR were administered, with a median of 3 cycles per
patient (16). Of 7 primary CNSL patients, 2 had progressive disease
(PD). 5 patients achieved PR, 2 of them proceeded to consolidation
with whole brain radiotherapy. 1 patient remains in PR (14.9 months)
and 1 died due to progressive disease (PD) (17.9 months). Of 3 un-
consolidated patients, 1 remains in PR (21.8 months) and 2 had PD
(21.7 and 12.2 months). Of 6 secondary CNSL patients, 1 patient died
due to pneumonia at day 6 of treatment. Of 5 evaluable patients, 1
patient had progressive disease (PD). 4 patients had achieved PR and
proceeded to autoSCT. 2 of them achieved and remain in complete
remission (CR) (34.7 and 19.8 months) and 1 remains in PR (10.2
months). One patient died due to autoSCT toxicity. Grade 35 adverse
events occurred in 54% of patients. After a median follow up of 21.7
months (95% CI 14.922.7), median OS was not reached. Among pa-
tients who responded to TEDDIR, the median PFS was 21.9 months
(95% CI 13.121.9).
Conclusions. In R/R secondary CNSL, TEDDIR may be used as a
bridge to autoSCT with curative intent. The regimen may induce
responses in some patients with R/R primary CNSL.
Keywords: Combination Therapies, Aggressive Bcell nonHodgkin
lymphoma
No conflicts of interests pertinent to the abstract.
TEDDIR outcomes in CNS lymphoma patients (n =13)
414
-
SUPPLEMENT ABSTRACTS
322 |OUTCOME OF PATIENTS WITH NEWLY DIAGNOSED
PRIMARY CNS LYMPHOMA AFTER HIGHDOSE METHOTREXATE
FOLLOWED BY CONSOLIDATION WHOLEBRAIN
RADIOTHERAPY AND CYTARABINE
P. Piriyakhuntorn
1
, T. Rattanathammethee
1
, S. Hantrakool
1
, C. Chai
Adisaksopha
1
, E. Rattarittamrong
1
, A. Tantiworawit
1
, L.
Norasetthada
1
1
Chiang Mai University, Division of Hematology, Department of Internal
Medicine, Faculty of Medicine, Chiang Mai, Thailand
Introduction: Current treatment of primary CNS lymphoma (PCNSL)
is a highdose methotrexate (HDMTX)based polychemotherapy.
The addition of cytarabine to HDMTXbased chemotherapy im-
proves clinical outcomes, however the combination therapy increases
toxicity. Sequential chemotherapy may decrease toxicity without
altering efficacy. This study aimed to analyze efficacy and safety of
sequential chemotherapy and cranial radiation for newly diagnosed
PCNSL patients.
Methods: This was a single center, retrospective cohort study
of consecutive newly diagnosed immunocompetent PCNSL patients
treated with HDMTX (5 cycles of 3 g/m
2
every 2 weeks) followed
by consolidation WBRT (total 46 Gy) and cytarabine (2 cycles of
3 g/m
2
/d for 2 days every 3 weeks) from January 2013 to
December 2020. Initial WBRT before HDMTX was allowed in pa-
tients with Karnofsky performance status less than 70%. Primary
outcome was progressionfree survival (PFS). Key secondary out-
comes were response rate, treatmentrelated toxicity, and overall
survival (OS).
Results: Of 41 patients, 25 patients had complete response (CR) and
10 patients had partial response, which inferred to an overall response
rate (ORR) of 85.4% and a CR rate of 60.9%. More than 90% of patients
were able to tolerate and complete HDMTX. Twentyone patients
(51.2%) received initial WBRT before chemotherapy. The incidence of
grade 3 hematologic and nonhematologic toxicities were 4.8% and
17.1%, respectively. Treatmentrelated mortality rate was 2.4%. There
was no difference in toxicity between patients with age <60 and 60
years. At the median followup duration of 39.8 months, median PFS
was 35.2 months (95%CI 12.4 69.3) and median OS was 46.5 months
(95%CI 21.8 NR).
Conclusion: Highdose methotrexate followed by consolidation
wholebrain radiotherapy and cytarabine has acceptable efficacy,
great tolerability, and low toxicity in newly diagnosed PCNSL patients.
EA previously submitted to EHA 2021.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Extranodal
nonHodgkin lymphoma, Combination Therapies
No conflicts of interests pertinent to the abstract.
323 |FOTEMUSTINEBASED THERAPY IN COMBINATION
WITH RITUXIMAB AS FIRSTLINE INDUCTION CHEMOTHERAPY
FOLLOWED BY WBRT FOR NEWLY DIAGNOSED PCNSL: A
PROSPECTIVE PHASE II TRIAL
J. Wu
1
, F. Gao
1
, L. Zhang
1
, X. Li
1
, L. Li
1
, Z. Sun
1
, X. Wang
1
, X. Fu
1
, X.
Zhang
1
, M. Zhang
1
1
The first affiliated Hospital of Zhengzhou University, Oncology
Department, Zhengzhou, China
Aim: To evaluate the safety, efficacy, and feasibility of the rituximab,
fotemustine, pemetrexed and dexamethasone (RFPD) regimen fol-
lowed by wholebrain radiotherapy (WBRT) for primary central
nervous system lymphoma (PCNSL) patients.
Methods: A prospective, singlecentre, phase II clinical trial was
conducted. Patients with newly diagnosed PCNSL were diagnosed at
the First Affiliated Hospital of Zhengzhou University from July
2018 to July 2020. The RFPD regimen consisted of rituximab (375
mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed
(600 mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D15).
SUPPLEMENT ABSTRACTS
-
415
Then, WBRT was implemented based on the patient's condition
(NCT04083066).
Results: Thirty patients were included. After two cycles, the objective
response rate (ORR) was 96.4% (27/28, 26 PR, 1 CR, 0 SD, 0 PD, and 2
censored) and the disease control rate (DCR) was 96.4% (27/28). After
four cycles, the ORR was 71.4% (15/21, 5 PR, 10 CR, 1 SD, 5 PD, 7 NR,
and 2 censored) and the DCR was 76.2% (16/21). After WBRT, the
ORR was 72.8% (8/11, 3 PR, 5 CR, 1 SD, and 2 PD) and the DCR was
81.8% (9/11). The median progressionfree survival (PFS) was 20.3
months (95% CI: 5.235.4). The median overall survival (OS) was 22.0
months (95% CI: 16.127.9). The grade IIIIV toxicities were mainly
leukopenia (20.0%), thrombocytopenia (23.3%) and anaemia (10.0%).
Conclusion: Fotemustinebased therapy in combination with ritux-
imab chemotherapy followed by WBRT can improve outcomes with
PFS and OS benefits and has better tolerability for newly diagnosed
PCNSL patients.
The research was funded by: The research was funded by the
Natural Science Foundation of Henan Province (No. 162300410304).
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemo-
therapy, Combination Therapies
No conflicts of interests pertinent to the abstract.
324 |FRACTIONATED TOTALBODY IRRADIATION AND
CYCLOPHOSPHAMIDE FOLLOWED BY AUTOLOGOUS STEM
CELL SUPPORT IN PATIENTS WITH TCELL LYMPHOBLASTIC
LYMPHOMA
M. Zhang
1
, R. X. Fu
1
, R. J. Ge
1
, C. Z. Sun
1
, F. F. Nan
1
1
The first affiliated Hospital of Zhengzhou University, Oncology
Department, Zhengzhou, China
Purpose: To evaluate a treatment regimen of fractionated total body
irradiation (TBI) and cyclophosphamide (CTX) followed by autologous
stemcell transplantation (ASCT) in patients with Tcell lymphoblastic
lymphoma.
Patients and Methods: 14 patients with Tcell lymphoblastic lym-
phoma received 10.0 Gy of fractionated TBI, and CTX 60 mg/kg/day
for two days (120mg/kg total), followed by infusion of autologous
hematopoietic stem cells.
Results: All of 14 patients are alive an average of 15 (range, 1.7 to
52.3) months after transplant. The 2year KaplanMeier (KM) esti-
mates of survival, progression survival (PFS) for all 14 patients were
75.2%, 58.4%, respectively. Eight (57.14%) patients had ongoing CRs
at the last disease assessment before the data cutoff. The median
time to achieve a sustained neutrophil count greater than 0.5 10
9
/L
was 12 days (range, 10 to 21).
Besides, one patients progressed after ASCT were eligible to
undergo chimeric antigen receptor Tcell therapies.
Conclusion: Improved OS and lower relapse risk were observed
following TBI plus cyclophosphamide. We therefore recommend
TBI plus cyclophosphamide following autologous stemcell
transplantation for patients with Tcell lymphoblastic lymphoma
who can't receive allogeneic HSCT.
The research was funded by: National Science and Technology
Major Project of China (Grant NO. 2020ZX09201009)
Keywords: Aggressive Tcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
325 |COMBINATION OF DECITABINE AND MODIFIED DHAP
REGIMEN: A POTENTIAL SALVAGE REGIMEN FOR RELAPSED/
REFRACTORY DIFFUSE LARGE BCELL LYMPHOMA AFTER
SECONDLINE TREATMENT FAILURE
J. Hu
1
, X. Wang
1
, M. Zhang
1
, Q. Chen
1
, X. Zhang
1
1
Department of Oncology, The First Affiliated Hospital of Zhengzhou
University, No.1 Jianshe East Road, Zhengzhou, Henan, China,
Department of Oncology, Zhengzhou, China
Objective: The prognosis for patients with relapsed or refractory
diffuse large Bcell lymphoma (R/RDLBCL) after secondline treat-
ment failure is extremely poor. This study prospectively observed the
efficacy and safety of decitabine with a modified cisplatin, cytarabine,
and dexamethasone (DHAP) regimen in R/RDLBCL patients who
failed secondline treatment.
Methods: Twenty R/RDLBCL patients were enrolled and treated
with decitabine and a modified DHAP regimen. The primary endpoints
were overall response rate (ORR) and safety. The secondary end-
points were progressionfree survival (PFS) and overall survival (OS).
Results: ORR reached 50% (complete response (CR) rate, 35%), five
patients (25%) had stable disease (SD) with disease control rate (DCR)
of 75%. Subgroup analysis revealed patients over fifty years old had a
higher CR rate compared to younger patients (p=0.005), and relapsed
patients had a better CR rate than refractory patients (p=0.031).
Median PFS was 7 months (95% confidence interval (CI), 5.18.9
months). Median OS was not achieved. Oneyear OS was 59.0% (95%
CI, 35.5%82.5%), and twoyear OS was 51.6% (95% CI, 26.9%76.3%).
The main adverse events (AEs) were grade 3/4 hematologic toxicities
such as neutropenia (90%), anemia (50%), and thrombocytopenia
(70%). Other main nonhematologic AEs were grade 1/2 nausea/vom-
iting (40%) and infection (50%). No renal toxicity or death occurred.
Conclusion: Decitabine with a modified DHAP regimen can improve
the short response and prognosis of R/RDLBCL patients with good
tolerance to AEs, suggesting this regimen has potential as a possible
new treatment option for R/RDLBCL patients after secondline
treatment failure. (identifier: NCT03579082)
The research was funded by: Grant No. 81700187, 82070210
and 2020ZX09201009
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemo-
therapy, Ongoing Trials
No conflicts of interests pertinent to the abstract.
416
-
SUPPLEMENT ABSTRACTS
326 |SALVAGE RADIOTHERAPY ASSOCIATES WITH DURABLE
RESPONSE FOR A SUBSET OF PATIENTS WITH LIMITED STAGE
REFRACTORY DIFFUSE LARGE BCELL LYMPHOMA
J. H. Miller
1
, M. Gilbertson
1
, M. P. MacManus
2
, A. Wirth
2
, S. S. Opat
1
G. P. Gregory
1
1
Monash Health, Monash Haematology, Melbourne, Australia,
2
Peter
MacCallum Cancer Centre, Radiation Oncology, Melbourne, Australia
Introduction. Despite favourable outcomes with chemo-
immunotherapy for the majority of patients with diffuse large Bcell
lymphoma (DLBCL), approximately onethird of patients experience
relapsed or refractory disease portending poor prognosis. Patients
ineligible for treatment intensification with salvage chemotherapy
may be offered palliative chemotherapy or radiotherapy, and in the
setting of singlesite progression, salvage radiotherapy with curative
intent. There remains a paucity of evidence for the latter with no
randomised clinical trials or large series reported in the literature.
The study was conducted to assess the outcomes of patients treated
with salvage radiotherapy for limited stage relapsed / refractory
DLBCL (rrDLBCL) at Monash Health, Australia, to determine its
utility and inform future treatment algorithms.
Methods. DLBCL cases (867 patients) diagnosed per WHO criteria
at Monash Health, Melbourne, Australia, between 1996 2019
within the Haematology Database were analysed. Adult patients
with rrDLBCL (including transformed indolent lymphoma) treated
with salvage radiotherapy alone with curative intent were
included in the study. Patients with inadequate clinical information
or follow up data available or those in whom radiotherapy was
administered as consolidation or clearly palliative intent were
excluded.
Results. From January 1996 December 2019, 18 eligible patients
were identified for inclusion in the study (12 refractory and 6
relapsed). A further 14 patients were excluded due to radiotherapy
for clearly palliative intent (n =7), CNS relapse (n =5), consolidation
(n =1) or prior indolent lymphoma (n =1). Median age at radio-
therapy commencement for the study population was 71 years (range
4283). 11/18 had biopsyproven refractory disease, a further 3/18
had inconclusive biopsy with high suspicion of active disease on im-
aging and remaining patients were treated on basis of high clinical
suspicion from PET imaging with sites not amenable to biopsy. Me-
dian radiotherapy dose was 42 Gy (range 1050). After a median
follow up of 14 months (range 164), 11/18 patients progressed
(Fig. 1) after a median of 2 months (range 020). 7/18 (39%) patients
remain in an ongoing remission without any progression events after
a median of 29 months (range 1364). Of the primary refractory
subset, 4/12 (33%) remain free from progression with a median
follow up of 32 months (range 1364).
Conclusion. Salvage radiotherapy with curative intent confers
meaningful disease control for a subset of patients with limited stage
rrDLBCL. Despite the small sample size and retrospective nature of
the study, we conclude salvage radiotherapy should be considered a
treatment option for patients ineligible for salvage chemotherapy in
cases of single site rrDLBCL. These findings warrant further clinical
investigation.
Keywords: Radiation Therapy
No conflicts of interests pertinent to the abstract.
327 |EFFICACY OF SALVAGE RADIOTHERAPY IN PATIENTS
WITH RESIDUAL OR RECURRENT DIFFUSE LARGE BCELL
LYMPHOMA
G. Cosman
1
, S. Dickson
2
, V. Chin
3
, S. Thompson
3
, S. Gupta
2
, Y. Chin
1
1
St George Hospital, Radiation Oncology, Sydney, Australia,
2
Calvary
Mater Hospital, Radiation Oncology, Newcastle, Australia,
3
Prince of
Wales Hospital, Radiation Oncology, Sydney, Australia
Introduction: Residual or recurrent diffuse large Bcell lymphoma
(DLBCL) following treatment with systemic chemotherapy is usually
treated with systemic therapy ±autologous stem cell trans-
plantation. Single, or limited sites of residual or recurrent disease
may however be treated with external beam radiotherapy (EBRT).
We are presenting our results of patients with residual or recurrent
DLBCL treated with salvage EBRT alone to assess its efficacy as a
salvage technique.
Methods: Patients diagnosed with DLBCL and treated with systemic
chemotherapy who had either persistent or recurrent disease were
retrospectively reviewed from databases across three tertiary hospi-
tals in New South Wales, Australia. Inclusion criteria were patients
aged 18 years old, diagnosis of DLBCL made between 20082016,
received first line chemotherapy, residual or recurrent disease on post
FIGURE 1 Eventfree survival from radiotherapy
commencement
SUPPLEMENT ABSTRACTS
-
417
chemotherapy fluorodeoxyglucose positron emission tomography
(FDG PET) scan, and curative intent salvage EBRT with dose 30Gy.
The primary outcome was freedom from treatment failure (FFTF) post
salvage radiotherapy. Secondary outcomes included local control and
overall survival post salvage radiotherapy. Survival was calculated
from the date of radiotherapy commencement to the date of last
followup.
Results: 46 patients met the inclusion criteria. Median age was 68
years (range, 1986 years). Just over half the patients had IPI score of
3 (51%) and 80% had bulky disease at initial diagnosis. The majority
of patients received 6x cycles of RCHOP chemotherapy (61%).
Median radiotherapy dose delivered was 40 Gy (range, 3046 Gy).
FFTF was achieved in 27 patients (59%) with a median followup of
54 months. Local control rate and 3year overall survival post salvage
EBRT were 80% and 59%, respectively.
Conclusion: EBRT is an effective salvage technique for DLBCL pa-
tients with localised persistent or recurrent PET positive disease post
systemic chemotherapy, if safely encompassable by radiotherapy
fields. The challenge for the future is to determine which group of
patients have micrometastatic disease at conclusion of chemotherapy
as current functional imaging is insufficient.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Radiation
Therapy
No conflicts of interests pertinent to the abstract.
328 |PIXANTRONE (PIX) IN RELAPSED/REFRACTORY DIFFUSE
LARGE BCELL LYMPHOMA (R/R DLBCL). REAL LIFE EXPERIENCE
IN 27 PATIENTS
A. Greco
1
, L. Tonialini
1
, P. R. Scalzulli
2
, G. De Santis
3
, E. Prete
1
, E. La
Rosa
1
, N. Cascavilla
2
, G. Tarantini
3
, V. Pavone
1
1
Pia Fondazione Card. G. Panico Hospital, Unit of Hematology, Tricase,
Italy,
2
Casa Sollievo della Sofferenza Hospital, Unit of Hematology, San
Giovanni Rotondo, Italy,
3
Monsignor Raffaele Dimiccoli Hospital, Unit of
Hematology, Barletta, Italy
Introduction: Treatment of relapsed/refractory (R/R) diffuse large B
cell lymphoma (DLBCL) represents an unmet clinical need due to the
lack of standard therapeutic options. Pix is an azaanthracenedione,
approved in Italy for the treatment of R/R DLBCL. Has been shown to
have antitumour activity but well tolerated with significantly
reduced cardiotoxicity. The main objective was to evaluate the ac-
tivity of this regimen in a large series of R/R DLBCL patients in a real
life setting on behalf of the Lymphoma working party of the Apulian
Hematological Network (REP).
Methods: This is a retrospective study on patients with R/R DLBCL
diagnosed from 2009 through 2020 in three hematological depart-
ment of REP. We included only patients treated with Pix as third (3L)
or fourth line (4L) from 2019 through 2020.
Results: We evaluated 27 patients (12 males and 15 females) treated
with pixantrone (13 relapsed and 14 refractory) for a median of 4
cycles (range 1–6). 59% of patients receiving treatment as third line.
The median age of patients receiving PIX was 71 years (interquartile
range 43–88) and 63% had a CIRS score >6. 8 patients were diag-
nosed as evolved by low grade lymphoma, 2 as double expressor, and
1 as doublehit DLBCL. 62% of patients had a germinal center Bcell
like (GCB) subgroups. The median duration of follow up was 8.3
months. The overall response rate was 66% with complete response
rate of 33%; 40% of patients eligible for transplant used pix as bridge
to transplant. The median duration of response was 5,8 months. No
patients had grade IV adverse events, which caused drug discontin-
uation or cardiotoxicity.
Conclusion: Our data documented drug efficacy that is satisfactory
for this highrisk subset of patients with an acceptable toxicity pro-
file. Most patients who received pix were older and with elevated
CIRSscore, which suggests the regimen may be favored also in frail
patients and transplantineligible population. Pix could be one of the
most appropriate agents to bridge patients to CARTcell therapy
based or to Transplant on its capacity to achieve rapid remission and
with safety profile
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemotherapy
No conflicts of interests pertinent to the abstract.
329 |RGDP SCHEDULE IN PATIENTS WITH REFRACTORY OR
RELAPSED BCELL NONHODGKIN LYMPHOMA (BNHL)
J. Rovira
1
, E. GonzálezBarca
2
, J. M. Sancho
3
, N. Kelleher
4
, M.
Rodríguez
5
, L. Fox
6
, R. Parody
2
, S. Martin
1
, A. Vicent
1
, J. Villarroel
2
, C.
de la Fuente
3
, J. M. Ribera
3
, A. Sureda
2
, L. Escoda
1
1
Institut Català Oncologia, Hospital Joan XXIII, Universitat Rovira i Virgili,
Hematology, Tarragona, Spain,
2
Institut Català Oncologia, Hospital Duran
i Reynals, Universitat de Barcelona, Hematology, L'Hospitalet de
Llobregat, Barcelona, Spain,
3
Institut Català d'Oncologia, Hospital
Germans Trias i Pujol, Hematology, Badalona, Spain,
4
Institut Català
d'Oncologia, Hospital Trueta, Hematology, Girona, Spain,
5
Institut Català
d'Oncologia, Hospital Verge de la Cinta, Hematology, Tortosa, Spain,
6
Hospital Universitari Vall d'Hebron, Hematology, Barcelona, Spain
Introduction: Despite longterm responses to firstline immunoche-
motherapy 3040% patients with Bcell lymphomas (BNHL) have
relapsed/refractory (R/R) disease. Autologous stemcell transplant
(SCT) remains the standard of care, the optimal choice of salvage
therapy being still unknown. RGDP [rituximab 375 mg/m
2
iv, gem-
citabine 1000 mg/m
2
iv (2 days), cisplatin 75 mg/m
2
iv and dexa-
methasone 40 mg orally (4 days) every 21 days] has shown similar
effectiveness compared to other schemes with less toxicity and al-
lows adequate mobilization of stem cells to peripheral blood with the
addition of GCSF.
Patients and Methods: Retrospective study of efficacy, toxicity and
stemcell mobilization capacity of RGDP as a salvage treatment in R/
R BNHL patients treated between 2018 and 2020 in 6 centers of
Catalonia.
418
-
SUPPLEMENT ABSTRACTS
Results: A total of 57 patients (41M:16F, median age at RGDP rescue
of 55 years [2276]) were included: 36 diffuse large Bcell lymphoma
(DLBCL), 11 other aggressive BNHL and 10 follicular lymphoma; 10
DLBCL transformed from an indolent lymphoma. 81% of patients
received RGDP as 2
nd
line. Median time from diagnoses to RGDP
administration was 10 months (2175) and most of the patients
(56%) received 3 cycles. Grade 34 toxicity was observed in 42% of
cases, mostly hematological (table). Hospital admission was required in
18% of cases with a median stay of 7 days. Main reason for admission
was infectious complications (42% neutropenic fever) despite pro-
phylactic GCSF in 85% of cases. Response was: complete remission
(CR) 18 (32%), partial remission 11 (19%), progression 28 (49%).
Mobilization with GCSF (10 µg/Kg/12h, median 5 days) was carried
out after 3
rd
RGDP cycle. Most patients (n =20, 80%) required 1 day of
apheresis, 26% (n =7) plerixafor use and the median CD34/Kg was 4
x10
6
(2,215,3). Only 2 patients (3,6%) showed inadequate mobiliza-
tion. Only 21 patients of 55 candidates (38%) reached the autoSCT
procedure, 6 patients despite RGDP refractoriness (69% in CR).
70% nonSCT patients were refractory. Median days of neutrophil and
platelet engraftment were 10 (718) and 11 (814), respectively. Four
patients proceeded to alloSCT and 10 received CART cell therapy (8
no SCT and 2 relapses post autoSCT). 2year progression free and
overall survival from RGDP were 22 and 36%, respectively.
Conclusion: RGDP can be used as a successful mobilization (plus G
CSF) and welltolerated salvage regimen for R/R BNHL patients
candidates to autoSCT with similar tumor reduction efficacy than
other schemes.
Table: Patient treatment characteristics and RGPD toxicity
(n =57)
Previous RGDP treatment (%)
1 81
2 10
3 9
RGDP cycles (%)
1 14
2 25
3 56
4 5
RGDP toxicity (%)
Grade 12 81
Gastrointestinal 41
Fatigue 38
Thrombosis 6
Hematological 13
Anemia 6
Neutropenia 6
Thrombocytopenia 8
(Continues)
(Continued)
Previous RGDP treatment (%)
1 81
2 10
3 9
Grade 34 42
Gastrointestinal 2
Fatigue 5
Neurological 2
Hematological 91
Anemia 14
Neutropenia 18
Thrombocytopenia 50
Figure: Progression free survival (PFS) and Overall survival
(OS) from RGDP salvage treatment
EA previously submitted to regional or national meetings (up to
1000 attendees).
Keywords: Chemotherapy, Stem Cell Transplant
No conflicts of interests pertinent to the abstract.
330 |POLATUZUMAB VEDOTIN PLUS BENDAMUSTINE AND
RITUXIMAB IN PATIENTS WITH RELAPSED/REFRACTORY
DIFFUSE LARGE BCELL LYMPHOMA IN THE REAL WORLD
P. Vodicka
1
, K. Benesova
1
, A. Janikova
2
, V. Prochazka
3
, D. Belada
4
, H.
Mocikova
5
, K. Steinerova
6
, J. Duras
7
, J. Karban
1
, V. Hanackova
3
, A.
Sykorova
4
, A. Obr
3
, M. Trneny
1
1
Charles University and General University Hospital, First Department of
Medicine, Prague, Czech Republic,
2
Faculty of Medicine, Masaryk
University and University Hospital, Department of Haematology and
Oncology, Brno, Czech Republic,
3
Faculty of Medicine and Dentistry,
Palacky University and University Hospital, Department of Haemato
SUPPLEMENT ABSTRACTS
-
419
Oncology, Olomouc, Czech Republic,
4
Faculty of Medicine, Charles
University and University Hospital, 4th Department of Internal Medicine
Haematology, Hradec Kralove, Czech Republic,
5
Third Faculty of Medi-
cine, Charles University and University Hospital Kralovske Vinohrady,
Department of Internal Medicine Haematology, Prague, Czech Republic,
6
Faculty of Medicine, Charles University and University Hospital,
Department of HaematoOncology, Pilsen, Czech Republic,
7
Medical
Faculty of the Ostrava University and University Hospital, Department of
Haematology, Ostrava, Czech Republic
Introduction. The treatment combination of polatuzumab vedotin,
bendamustine and rituximab (PolaBR) has been recently approved
for transplantineligible patients with relapsed/refractory diffuse
large Bcell lymphoma (R/R DLBCL). However, the number of pa-
tients treated in the GO29365 trial (NCT02257567) including the
extension cohort was limited, and more data is needed. We retro-
spectively analysed the outcome of 21 patients treated with pola-
tuzumab vedotin to determine the efficacy and safety of this
treatment regimen in the realworld settings.
Methods. A total of 21 patients were scheduled to receive 6 cycles
of PolaBR every 21 days (polatuzumab vedotin 1.8 mg/kg; ritux-
imab 375 mg/m
2
; bendamustine 70 mg/m
2
in 7 cases and 90 mg/m
2
in 13 cases; no bendamustine in 1 case). Data of all patients were
entered into the database of the NiHiL project (NCT03199066).
Treatmentrelated adverse events (AEs) were classified according to
the Common Terminology Criteria for Adverse Events. Primary
endpoint of the study was the overall survival (OS), secondary
endpoints included the progressionfree survival (PFS), and
response rate to the therapy.
Results. Median age at relapse was 67 years (range 3585 years).
Sixteen (76.2%) patients were diagnosed with clinical stage IIIIV, 10
(47.6%) patients with performance status according to ECOG 2, 16
(76.2%) patients with elevated levels of lactate dehydrogenase and
with extranodal involvement, 15 (71.4%) patients with high
intermediate or highrisk International Prognostic Index. Patients
were pretreated with median of 3 previous lines of therapy (range
27) including autologous stem cell transplant in 6 (28.6%) cases.
Median number of PolaBR cycles was 2 (range 16), 5 (23.8%) pa-
tients received all intended 6 cycles of the therapy. Median OS from
relapse was 8.7 months, median PFS was 3.8 months, with a median
followup of living patients of 6.8 months. The overall response rate
was 33.3% (n =7), 5 (23.8%) patients reached complete remission, 2
(9.5%) patients reached partial remission. Stable disease was
detected in 2 (9.5%) cases, progressive disease (PD) in 9 cases
(42.9%). Grade 34 haematologic toxicities included neutropenia in 6
(28.6%) patients, thrombocytopenia in 8 (38.1%) cases, and anaemia
in 4 (19.0%) cases. Peripheral neuropathy was detected in one (4.8%)
patient, infections grade 34 in 5 (23.8%) cases. In 16 (76.2%) pa-
tients, the reason for early discontinuation of the treatment included
PD (n =8; 50.0%), followed by AEs (n =5; 31.3%), and intended
bridging to CART therapy (n =3; 18.8%).
Conclusions. The use of PolaBR regimen in the real world demon-
strates tolerable toxicity profile and efficacy in transplantineligible
patients with R/R DLBCL. Moreover, this regimen might represent
a perspective option as a bridge to CART therapy.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemo-
therapy, Immunotherapy
Conflicts of interests pertinent to the abstract
p. vodicka
Consultant or advisory role: Roche
A. Janikova
Consultant or advisory role: Roche
D. Belada
Consultant or advisory role: Roche
M. Trneny
Consultant or advisory role: Roche
331 |TIMETORESPONSE FOR PATIENTS WITH RELAPSED/
REFRACTORY AGGRESSIVE B CELL NONHODGKIN LYMPHOMA
TREATED WITH POLATUZUMABBASED THERAPY
M. E. Hughes
1
, S. D. Nasta
1
, J. N. Gerson
1
, J. Svoboda
1
, E. A. Chong
1
,
S. J. Schuster
1
, S. K. Barta
1
, K. W. Robinson
1
, D. J. Landsburg
1
1
University of Pennsylvania, Abramson Cancer Center, Philadelphia,
Pennsylvania, USA
Introduction: Knowledge of timetoresponse after initiation of ther-
apy (TTR) may influence treatment recommendations made to patients
(pts) with relapsed/refractory (R/R) aggressive B cell nonHodgkin
lymphoma (aBNHL) given the potential for rapid disease growth. If
reported in clinical trials, TTR is dependent upon the timing of
protocolspecified imaging response assessments (IRA) and does not
account for clinical response to therapy (Rc), which may precede
radiographic response (Rr). Here we report TTR and other response
related outcomes in pts with R/R aBNHL treated with polatuzumab
(pola).
420
-
SUPPLEMENT ABSTRACTS
Methods: Pts analyzed were those with nonBurkitt R/R aBNHL
diagnosed on most recent tissue biopsy and first treated with pola
at the University of Pennsylvania from 7/2019 to 12/2020. Rc was
defined as reduction in lymph node size on examination, resolution
of diseaserelated symptoms, normalization of lactate dehydroge-
nase (LDH) previously >2x upper limit of normal or disease
response on imaging performed for indication other than IRA. Rr
was assessed per Revised Response Criteria for Malignant Lym-
phoma. Timing of clinical/laboratory assessments and IRA were at
the discretion of the treating clinician. Data were censored on 3/1/
2021.
Results: Fifty pts were included in this analysis. Baseline clinico-
pathologic and treatment characteristics at time of pola initiation
are listed in Table 1. Nineteen pts (38%) were treated with the
intent to bridge to cellular therapies (CT). Median number of cycles
of pola received was 3. Rc was achieved by 18 pts (36%), Rr by 16
pts (32%) and the composite outcome of Rc or Rr (overall response,
[Ro]) by 24 pts (48%). IRA was not performed for 9 pts: 7 due to
proceeding to planned CT (5 with Rc) and 2 due to death not
attributed to aBNHL with ongoing Rc. The median TTRc, TTRr and
earliest of TTRc or TTRr (TTRe) were 21 d (range 741 d), 64
d (range 17137 d) and 22 d (767 d), respectively. Of 12 pts who
achieved Rc and had subsequent IRA performed, 8 achieved Rr.
Twelve pts stopped tx in remission: 7 pts due to proceeding to
planned CT, 3 due to toxicity (gastrointestinal in 2 pts and neu-
ropathy in 1 pt) and 2 pts due to choice. Excluding the 7 pts
proceeding to planned CT in remission, the estimated proportion of
pts with ongoing Rc and Rr at 180 d were 53% and 51%, respec-
tively. Of characteristics listed in Table 1, nonhigh grade B cell
histology and receipt of prior CD19directed chimeric antigen
receptormodified T cell therapy were significantly associated with
achievement of Ro; additionally, age 60 years, largest tumor
diameter 7.5 cm and disease refractory to most recent prior
therapy were significantly associated with shorter TTRe.
Conclusions: For R/R aBHL pts treated with pola at our institution,
frequently with the intention to bridge to CT, 48% achieved Rc or Rr
with median TTR of 22 d. These findings may further inform use of
pola in the standardofcare and investigational settings.
Keywords: Aggressive Bcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
M. E Hughes
Consultant or advisory role: AstraZeneca, Genzyme, Janssen, AbbVie,
Karyopharm
Research funding: Acerta
S. D Nasta
Consultant or advisory role: Morphosys, Merck
Research funding: Roche/Genentech, Millennium/Takeda, Pharma-
cyclics, ATARA, Forty Seven
J. N Gerson
TABLE 1Baseline characteristics
SUPPLEMENT ABSTRACTS
-
421
Consultant or advisory role: Pharmacyclics, Genentech, AbbVie
Research funding: Loxo
J. Svoboda
Consultant or advisory role: Seattle Genetics, BristolMyers Squibb,
Pharmacyclics, Imbrium Therapeutics, Genmab, Adaptive Bio-
technologies, ADC Therapeutics, Atara Biotherapeutics
Research funding: Celgene, Seattle Genetics, Pharmacyclics, Merck,
BristolMyers Squibb, Incyte
Educational grants: Imbrium Therapeutics
E. A Chong
Consultant or advisory role: Novartis, Tessa Therapeutics, Bristol
Myers Squibb, Kite/Gilead
S. J Schuster
Consultant or advisory role: Celgene, Nordic Nanovector, Novartis,
AbbVie, Acerta, Alimera Sciences, BeiGene, Juno Therapeutics, Loxo
Oncology, Tessa Therapeutics, Genetech/Roche, Research funding:
Novartis, Pharmacyclics, Adaptive Biotechnologies, Merck, Gene-
tech/Roche, Celgene, Juno Therapeutics, AbbVie, Incyte, TG Thera-
peutics, DTRM,
S. K Barta
Consultant or advisory role: Monsanto
Honoraria: Atara, Seattle Genetics, Janssen, Pfizer, Acrotech
Research funding: Seattle Genetics,
D. J Landsburg
Consultant or advisory role: Morphosys, Karyoparhm, Celgene
Research funding: Takeda, Curis, Triphase
Other remuneration: Karyopharm
332 |PET ORIENTED INTENSIFICATION AND MAINTENANCE
WITH RITUXIMAB IN FIRST LINE NONHODGKIN LARGE B CELL
LYMPHOMA (DLBCL)
L. Pezzullo
1
, G. Cassiordor0
1
, R. Rosamilio
1
, I. Ferrara
1
, S. Luponio
1
, B.
Serio
1
, C. Martorelli
1
, L. Mettivier
1
, R. Fontana
1
, R. Guariglia
1
, C.
Selleri
1
1
Salerno University, Hematology Division, Salerno, Italy
The addition of rituximab to induction chemotherapy improved the
outcome of patients with diffuse large Bcell lymphoma (DLBCL).
However, relapse prevention with antiCD20 antibody maintenance
therapy is not the standard in DLBCL lymphoma confirmed by
various randomized trials.
To study in patients who achieved an uncertain or unsatisfactory
response (PR or CRu guided by PET with a deauville score of 23
after induction therapy with RCHOP or similar chemotherpy) with
intensification therapy with rituximab (Rituximab 375 mg / m2 per
week for 4 weeks) followed by maintenance (rituximab 375 mg / m2
every 2 months for a total of 12 administrations or until any
progression or unacceptable toxicity) to assess whether we observe
an improvement in results in this cohort of patients.
From January 2014 to January 2021 we studied 75 consecutive
patients with DLBCL (45m and 30f, mean age: 65 years (range 2882
years); 37 ABC, 25 GC; 5 NOS; 5 Trich and 3 immunoblastic), treated
with RCHOP chemotherapy cycles or similar.
Of the 75 patients (with a median followup of 30 months) the ORR
was 77% (58/75 patients: CR 39; CRu 16 and PR 3); 7 NR (9%); 7 (9%)
died before completion of therapy and 3 (5%) has still on RCHOP
treatment. The total OS, PFS and EFS of this group projected at 54
months was respectively of 75%; 78% and 75%.
After induction therapy with RCHOP 58/75 patients (77%)
responded to treatment (39 CR; 16 CRu and 3 PR) and we considered
these patients to evaluate responses to intensification and mainte-
nance treatment with rituximab. oriented by the PET response at the
end of RCHOP.
Results: we treated 18/58 patients 31% of patients, 16 in CRu (final
PET score 23 deauville) and 2 in PR after RCHOP induction with
consolidation and maintenance with rituximab, 13 m and 5 f with
median age age 66 (range 4477) 8 ABC; 7 GC; 2 immunoblastic and
1 rich in T. No significant side effects were observed in this patient
group.
After a median followup of 40 months (range 888 months) 17/18
(94%) patients are in CR (only one patient relapsed after 18 months).
While after a median followup of 30 months of 40/58 patients in CR
after induction of RCHOP, 33 (83%) are in CR while 7 (17%) had a
relapse.
Observations of these 2 groups projected at 85 months were similar
for OS (94% and 93% respectively); while PFS and EFS were 94% and
82% in the maintenance or nonmaintenance groups, respectively.
Summary / Conclusion: these retrospective data, collected by our
center, demonstrate an improvement in PFS and EFS in patients with
RP or CRu with DLBCL compared to the literature in particular, an
overall advantage was noted for the DLBCL ABC subgroup per-
forming this treatment ( total patients DLBCL ABC and GC with OS
at 70 months 82% and 76% respectively).
This improvement may be due to consolidation and rituximab
maintenance therapy in the deuville 23 score cohort after R
CHOP induction (PEToriented treatment). A larger cohort of pa-
tients and a randomized trial are needed to confirm these pre-
liminary data
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
333 |INTRAVENOUS HIGH DOSE METHOTREXATE AS
CENTRAL NERVOUS SYSTEM (CNS) PROPHYLAXIS IN PATIENTS
WITH DIFFUSE LARGE B CELL LYMPHOMA (DLBCL) WITH HIGH
RISK FOR CNS PROGRESSION
J. A. Villarreal
1
, J. Rovira
2
, M. Franch
3
, M. Encuentra
1
, D. Blazevic
1
,
M. Rodriguez
4
, N. Kelleger
5
, S. Martín
2
, A. C. Oliveira
1
, E. Domingo
422
-
SUPPLEMENT ABSTRACTS
Domenech
1
, J. M. Ribera
3
, A. Sureda
1
, J. M. Sancho
3
, L. Escoda
2
, E.
GonzálezBarca
1
1
Institut Català d'Oncologia, Hospital Duran i Reynals, Institut
d'Investigació Biomèdica de Bellvitge (IDIBELL), Hematology,
L'Hospitalet de Llobregat, Barcelona, Spain,
2
Institut Català d'Oncologia,
Hospital Universitari Joan XXIII, Hematology, Tarragona, Spain,
3
Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Institut de
Recerca contra la Leucèmia Josep Carreras, Universitat Autònoma de
Barcelona, Hematology, Badalona, Barcelona, Spain,
4
Institut Català
d'Oncologia, Hospital de Tortosa Verge de la Cinta, Hematology,
Tortosa, Tarragona, Spain,
5
Institut Català d'Oncologia, Hospital
Universitari de Girona Doctor Josep Truet, Institut d'Investigació
Biomèdica de Girona (IDIBGI), Universitat de Girona, Hematology,
Girona, Spain
Introduction: Despite improvement in survival in diffuse large Bcell
lymphoma (DLBCL), central nervous system (CNS) relapse represents
a clinical challenge. The most widely used CNS prophylaxis is intra-
thecal methotrexate, which arrives to the leptomeninges, but it has
limited value in DLBCL, which usually presents CNS parenchymal
involvement. Therefore, prophylaxis should include deeply penetrant
drugs such as intravenous highdose methotrexate (HDMTX). Our
aim was to evaluate the feasibility and efficacy of HDMTX in com-
bination with immunochemotherapy in patients with high risk criteria
for CNS progression.
Patients and Methods: Retrospective study of 47 patients, diag-
nosed from October 2016 to July 2020, in 5 hospitals of the Catalan
Institute of Oncology in Spain, who received CNS prophylaxis with
HDMTX (3 g/m
2
) and who were diagnosed of: DLBCL with high risk
criteria for CNS progression [CNS International Prognostic In-
dex (CNSIPI) 4, specific extranodal sites involvement: pericardial,
bone marrow, testes, uterine, breast]; or high grade lymphoma
double hit.
Results: Characteristics at diagnosis are summarized in the table.
Of note, median age: 53 years, CNSIPI 4: 42 (89%), high risk
extranodal sites involvement: 25 (53%), double hit: 7 (15%).
Treatment consisted of 3 cycles HDMTX alternating with 6 cycles
RCHOP (cycles 2,4,6): 35 patients; 2 cycles HDMTX alternating
with 6 cycles RCHOP (cycles 3,6): 4 patients; 6 cycles RCHOP
followed by 3 cycles HDMTX: 2 patients. Six patients with dou-
ble hit lymphoma were treated with 3 cycles HDMTX alternating
with 6 cycles DAREPOCH (cycles 2,4,6): 3 patients; 6 cycles DA
REPOCH followed by 2 cycles HDMTX: 3 patients. Seven (15%)
patients presented acute kidney injury after the first dose of
HDMTX, 3 (6.4%) grade 34, in whom HDMTX was stopped (in 1
patient RCHOP was delayed 14 days). All patients with DAR
EPOCH completed the planned doses. Other frequent toxicities
among 112 cycles of HDMTX were: neutropenia 8 (7%), anemia 6
(5.3%), neutropenic fever 4 (3.6%), and mucositis 3 (2.7%), mostly
grade 12. Eight (17%) patients stopped treatment before
completing their plan, 4 due to progression (one in CNS), 3 due to
infectious complications and 1 for unknown reason. Response was
evaluable in 45 patients: CR 34 (76%), PR 5 (11%), progression 6
(13%). With a median followup of 22 months, PFS was 62.7%
(95%CI 4877.4) and OS was 66.4% (95%CI 49.583.3). Three
(6.4%) patients progressed in CNS, two at 6 months and one at 10
months from diagnosis.
Conclusions: HDMTX is used as CNS prophylaxis in a young subgroup
of DLBCL patients. HDMTX alternating with systemic immunoche-
motherapy is feasible and can be administered safely in most cases,
being acute kidney injury the most frequent toxicity leading to
discontinuation. Nevertheless, 6% of patients had an early CNS
relapse. Therefore, new strategies should be investigated in this very
high risk population.
SUPPLEMENT ABSTRACTS
-
423
Figure: Progressionfree survival of 47 patients with high
risk of CNS progression treated with HDMTX
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemo-
therapy, Combination Therapies
No conflicts of interests pertinent to the abstract.
334 |SAFETY OF SAME DAY HDMTX WITH INDUCTION
THERAPY FOR DLBCL WITH CONCURRENT CNS DISEASE OR AS
PROPHYLAXIS FOR HIGH RISK OF CNS RELAPSE
B. Barlow
1
, C. D. Bodine
1
, H. Hatic
1
, G. Goyal
1
, A. Mehta
1
,
M. Narkhede
1
1
University of Alabama at Birmingham, Hematology/Oncology,
Birmingham, Alabama, USA
Background: Highdose methotrexate (HDMTX) at a dose between
2.5 to 5 gm/m
2
is commonly administered in conjunction with stan-
dard induction chemotherapy to patients with Diffuse Large B Cell
Lymphoma (DLBCL) at high risk of central nervous system (CNS)
relapse, as defined by the Lymphoma International Prognostic Index
(CNSIPI). Optimal timing of HDMTX in relation to induction
chemotherapy is unknown. A recent study suggested that HDMTX
intercalated with RCHOP cycles was associated with increased
toxicity and treatment delays without improvement in survival or
CNS relapse compared with end of treatment MTX (Wilson et al
2020). This retrospective study evaluates the toxicities and treat-
ment delays associated with HDMTX administered on day 1 of cy-
cles of chemoimmunotherapy.
TABLE 1Outcome of Day 1 HDMTX with induction Therapy (n=45)
424
-
SUPPLEMENT ABSTRACTS
Methods: This single center retrospective cohort study included 45
patients(pts) with DLBCL with concurrent CNS disease or at high risk
of CNS relapse who received HD MTX on day 1 of chemo
immunotherapy at our center. Data was abstracted from chart re-
view and included variables describing clinical and treatment char-
acteristics, time to MTX clearance, toxicities experienced and
treatment delays.
Results: 31 pts received HDMTX on the day of RCHOP chemo-
therapy, 6 pts received HDMTX on the day of REPOCH (Rituximab,
Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, and Predni-
sone) and 8 pts received HDMTX with RMiniCHOP (dose reduced
RCHOP). Same day HD MTX with chemoimmunotherapy was
associated with acute kidney injury (AKI; 1725%), treatment delays
>7 days (1317%), and grade 2 mucositis (1150%). The burden of
toxicities was numerically higher in patients treated with REPOCH
vs. RCHOP (Table 1). Clinical outcomes are summarized in Table 1
below.
Conclusion: In our heterogeneous population of pts, we describe that
the incidence of toxicities and treatment delays experienced with
same day HDMTX are higher with REPOCH than with RCHOP.
Comparative studies with intercalated or end of treatment MTX will
determine if the incidence of treatment delays, toxicities and de
escalations are higher with same day HDMTX administration.
EA previously submitted to ASCO 2021.
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
335 |RCODOXM/RIVAC IN HIGH RISK AND MYC MUTATED
DIFFUSE LARGE B CELL LYMPHOMAA SINGLE CENTRE
RETROSPECTIVE STUDY
S. L. Beverstock
1
, F. M. Scott
1
1
Western General Hospital, Department of Haematology, Edinburgh, UK
Introduction: Rituximab, cyclophosphamide, doxorubicin, vincristine,
prednisolone (RCHOP), treatment for diffuse large B cell lymphoma
(DLBCL), fails to achieve long term disease control in 50% patients
with a high (35) international prognostic index (IPI). Outcome post
RCHOP of double (DH) or triple hit (TH) disease, MYC rearrange-
ment concurrent with BCL2, BCL6 rearrangements or both, is also
poor with 5 year progression free survival (PFS) 27% and overall
survival (OS) 18%.
UK National Cancer Research Institute (NCRI) Phase 2 Study of
efficacy of 1st line rituximab, cyclophosphamide, vincristine, doxo-
rubicin, methotrexate, ifosfamide, etoposide, cytarabine (RCODOX
M/RIVAC) in high risk DLBCL (IPI 35) achieved 2 year PFS of
67.9%. Fluorescence in situ hybridisation (FISH) for MYC, BLC2,
BCL6 was done in 51.4% of patients so findings cannot necessarily be
extrapolated to high grade B lymphoma as per 2016 World Health
Organisation criteria.
Methods: We undertook a retrospective review of patients within
South East Scotland who received RCODOXM/RIVAC as initial
therapy for DLCBL with high risk features (IPI 35 or recurrent ge-
netic rearrangements by FISH) between 2014 and 2020. 35 patients
were identified. FISH analysis of biopsy was available in 91%: 51%
had a normal MYC, 11% had an isolated MYC translocation, 6% TH,
23% DH (17% MYC/BCL2; 6% MYC/BCL6. Immunoglobulin partner
gene status was unknown.
Results: Median age 59 years (range 24–73), 57% were male, 37%
were treated on over 65s protocol. 14 (40%) failed to complete
treatment due to: cytopenias (29%), neutropenic sepsis (21%), hep-
atoxicity (14%), progressive disease (PD) (8%), mucositis (8%).
Treatment delays occurred in 22 (63%), median duration of delay 16
days (range 357): infection accounted for 74%, delayed count re-
covery 13%, hepatotoxicity 9%. There were 2 treatment related
deaths.
Outcomes were similar to those observed in NCRI study: 24
(69%) achieved complete response (CR), 1 year OS 71%. 8 (23%) had
primary refractory disease (PRD), 7 (88%) of whom died of PRD. 3
(11%) responding patients relapsed: 1 achieved CR post salvage, 2
died of PD.
Impact of MYC status was variable: CR rate was 72% with
normal MYC, 79% if isolated MYC mutation, 75% in DH and 50% in
TH. Risk of PRD was higher if MYC abnormality detected: 17% with
normal MYC relapsed compared to 50% with a MYC abnormality.
Conclusion: RCODOXM/RIVAC proved effective in DH and TH
disease achieving OS of 77% at 2 year, benefit in other high risk
patients was less clear. Treatmentrelated toxicity in the real
world setting was significant; 40% of patients failed to complete
all 4 cycles and treatment delays were common. The local man-
agement guideline has subsequently been modified, deescalating
treatment to RCHOP for those without DH/TH or CNS
involvement.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Pathology and
Classification of Lymphomas, Chemotherapy
No conflicts of interests pertinent to the abstract.
336 |ZANUBRUTINIB, LENALIDOMIDE PLUS RCHOP (ZR
2
CHOP) AS THE TREATMENT FOR DIFFUSED LARGE BCELL
LYMPHOMA (DLBCL)
H. Zhu
1
, Y. Sha
1
, W. Wu
1
, R. Chen
1
, Y. Yang
2
, J. Qiu
2
, H. Mi
2
, C. Peng
2
,
C. Ding
3
, Z. Wang
4
, L. Fan
1
, W. Xu
1
, J. Li
1
1
The First Affiliated Hospital of Nanjing Medical University, Department
of Hematology, Nanjing, China,
2
Pukou division of Jiangsu Province
Hospital, Pukou CLL Center, Nanjing, China,
3
The First Affiliated Hospital
of Nanjing Medical University, Department of Nuclear Medicine, Nanjing,
China,
4
The First Affiliated Hospital of Nanjing Medical University,
Department of Pathology, Nanjing, China
SUPPLEMENT ABSTRACTS
-
425
Introduction: To evaluate the safety and efficacy of zanubrutinib,
lenalidomide plus RCHOP (ZR
2
CHOP) as the treatment for DLBCL
patients, we conducted this singlearm retrospective observational
study.
Methods: We enrolled patients aged 18 to 75 years old with high
risk DLBCL. Oral zanubrutinib was given continuously (160mg
twice daily) from Day 0, lenalidomide 25mg daily Day 17. Patients
were administered intravenously rituximab (375mg/m
2
Day 0),
cyclophosphamide (750mg/m
2
Day 1), doxorubicin (50mg/m
2
Day
1), vincristine (1.4mg/m
2
Day 1), and oral prednisone (50mg/day
Day 15). All patients were recommended to receive 6 cycles of
ZR
2
CHOP (R/R
2
CHOP were allowed in cycle 12 due to poor
physical condition at treatment) and patients older than 70 years
old were administered ZR
2
miniCHOP (Figure 1). ctDNA was
dynamically detected before treatment, after 3 and 6 cycles to
evaluate tumor mutational burden. The primary endpoint was
complete response ratio (CRR) after midterm and 6 cycles. The
secondary endpoint was overall response rate (ORR), ctDNA and
the number of adverse events (AE). AEs were graded based on
CTCAE (version 5.0).
Results: 10 DLBCL patients diagnosed in Pukou CLL Center were
enrolled in this cohort between July 2020 and February 2021, with 9
treatmentnaïve DLBCL and 1 Relapsed/Refractory DLBCL (PD after
4 cycles of bendamustine plus rituximab). The median age of patients
was 55 years old and all patients had ECOGPS 2. 1 patient (1/10)
was diagnosed as doublehit DLBCL and 7 patients (7/10) as double
expression. 8 patients were nonGCB and 2 were GCB. 7 patients (7/
10) were classified as highintermediate and highrisk group ac-
cording to NCCNIPI (Table 1). At data cutoff (1st March, 2021), the
median followup was five months (38 months) with all patients have
completed at least 3 cycles and midterm assessment could be con-
ducted. The ORR was 100.0%, with 9 patients achieved CR (9/10) and
1 patients achieved PR (1/10). ctDNA was dynamically detected in
five patients. The median number of baseline somatic mutation was 5
and all 5 patients showed undetectable ctDNA after 3 cycles. 4 pa-
tients have received 6 cycles, all of them achieved CR (4/4) and un-
detectable ctDNA (4/4) (Figure 1). The most common hematological
toxicity events were lymphocytes count decreased, neutrophil count
decreased, thrombocytopenia and anemia, with 34 level occurrence
rate was 70.0%, 30.0%, 20.0% and 20.0%. The most common non
hematological toxicity events were nausea and fatigue. One pa-
tients discontinued oral zanubrutinib and lenalidomide more than
seven days due to drug rash.
Conclusion: ZR
2
CHOP for highrisk DLBCL patients with fair
physical condition could achieve high CRR and high proportion of
earlystage undetectable ctDNA. The overall tolerability was under
control. ZR
2
CHOP could be one of the promising choices for the
treatment of highrisk DLBCL.
EA previously submitted to regional or national meetings (up to
1000 attendees) and EHA 2021.
The research was funded by: This study was supported by Fund
of National Natural Science Foundation of China (Grant No.
81970146), National Science Foundation of China International
Cooperation and Exchange Programme (Grant No. 81720108002),
National Science and Technology Major Project (Grant No.
2018ZX09734007) and Six Talent Peaks Project in Jiangsu Province,
2019 (Grant No. WSN001).
Keywords: Chemotherapy, Molecular Targeted Therapies, Combina-
tion Therapies
No conflicts of interests pertinent to the abstract.
TABLE 1Baseline Clinical Characteristics of DLBCL patients
426
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SUPPLEMENT ABSTRACTS
337 |PROGNOSTIC IMPACT OF NUTRITIONAL STATUS ON
DLBCL PATIENTS
C. Barros Lima
1
, B. Marques
1
, S. Duarte
1
, C. Afonso
1
, D. Neves
1
, A.
Lai
2
, M. Julião
2
, L. Ruzickova
1
, J. Carda
1
, M. Gomes
1
, A. Cipriano
2
, A.
Espadana
1
1
Centro Hospitalar e Universitário de Coimbra, Hematology Department,
Coimbra, Portugal,
2
Centro Hospitalar e Universitário de Coimbra,
Pathology Department, Coimbra, Portugal
Introduction: The prognostic impact of body mass index (BMI) in
diffuse large B cell Lymphoma (DLBCL) patients is controversial, as
some studies showed a survival benefit for higher BMI while others
showed no correlation or even a detrimental effect on survival. On
the other hand, studies regarding nutritional status impact on pa-
tients outcome have shown that lower Prognostic Nutritional Index
(PNI) scores are related to lower Progression Free Survival (PFS) and
Overall Survival (OS).
Aim: Evaluate the impact of BMI and PNI at diagnosis on OS and PFS
on a cohort of patients with DLBCL, NOS.
Methods: Retrospective data from patients (pts) with DLBCL,
NOS, diagnosed between 2010 2019. BMI was calculated as
weight/height2. PNI was calculated as 10xserum albumin (g/dL)
+0.005xabsolute lymphocyte count. Two groups were defined
for both variables for statistical analysis using a ROC curve to
discriminate outcomes (OS and PFS). A p value less than
0.05 was considered statistically significant. Univariate and multi-
variate analysis was performed to evaluate the impact on the
outcomes.
Results: A total of 335 patients were diagnosed with DLBCL, NOS,
with a median age of 65 yrs; 177 (53%) were male and 248 (74%) had
an ECOGPS 01. The BMI was <18.5 Kg/m2 on 8 pts (2.4%), 18.5
24.9 Kg/m2 on 135 (40.3%), 25 29.9 Kg/m2 on 82 (24.5%) and 30
Kg/ m2 on 43 (12.8%).
Using ROC curves, the cutoffs for BMI and PNI were 31 Kg/m2 and
38, respectively. Patients with higher BMI (31 Kg/m2) showed
better ECOGPS (p =0.03) and a lower Ann Arbor stage (p =0.036).
After 5 years of follow up, patients with lower BMI (<31 Kg/ m2) had
a non statistically difference in both PFS (52% vs 40%, p =0,49) and
OS (58% vs 50%, p =0,75) vs higher BMI.
PNI was significantly higher on male pts (p =0.02), patients under 65
years old (p =0.004), AnnArbor stage III (p =0.001), ECOGPS 01
(p <0.001) and BMI 31 Kg/m2 (p =0.022). At 5 years, patients with
higher PNI (>38) showed a higher PFS (63% vs 32%, p <0,001) and
OS (68,5% vs 37,5%, p <0,001), both statistically relevant. However,
when taking into account other variables, namely age, ECOGPS, IPI,
AnnArbor stage, B symptoms and low albumin, PNI impact on PFS
(p =0.065) and OS (p =0.072) was not statistically significant,
Conclusion: In our cohort, BMI and PNI did not have a significant
impact in PFS or OS although the impact of PNI on PFS remained close
to being significant. More studies are needed to evaluate the impact of
nutritional status and its relevance for inclusion of PNI as a tool for
clinical evaluation and risk assessment in patients with DLBCL, NOS.
Keywords: Other
No conflicts of interests pertinent to the abstract.
338 |PROGNOSTIC VALUE OF RED CELL DISTRIBUTION
WIDTH AT DIAGNOSIS (RDW) IN DIFFUSE LARGE BCELL
LYMPHOMA.
J.M. Raya
1
, P. LópezGarcía
2
, C. D. Reyes
2
, M.J. RodríguezSalazar
1
,
C. De Bonis
1
, B. GonzálezGonzález
1
, M. T. HernándezGarcía
1
,
S. Lakhwani
1
1
Hospital Universitario de Canarias, Hematology, La Laguna, Spain,
2
Universidad de La Laguna, Facultad de Ciencias de la Salud, sección
Medicina, La Laguna, Spain
FIGURE 1 Treatment Scheme of ten DLBCL patients.
SUPPLEMENT ABSTRACTS
-
427
Diffuse large Bcell lymphoma (DLBCL) constitutes approximately
30% of adult nonHodgkin lymphomas in developed countries, and
even a higher percentage in developing countries. RCHOP is the
standard chemotherapy regimen and 5year overall survival ranges
from 60 to 70%. Main prognosis factors associated with outcome are
gathered into the International Prognosis Index (IPI) but in the last
years some other factors have been investigated in order to
discriminate highrisk subgroups of patients. The red cell distribution
width (RDW) has been studied as a possible prognostic factor in
DLBCL and other malignancies. Our aim was to analyze if elevated
RDW (>15%) may help to differentiate patients affected by DLBCL
with a worse overall survival.
We studied 53 patients (male 51%, mean age 66 years, range 1891)
with a diagnosis of DLBCL treated in our institution between 2010 and
2015. At diagnosis, RDW was elevated in 21 patients (39,6%) and
lactate dehydrogenase was high in 32 cases (60,4%). Distributed ac-
cording to Ann Arbor, 3 patients (5,7%) were in stage 1, 8 patients in
stage 2 (15,1%), 14 patients in stage 3 (26,4%) and 28 patients in stage 4
(52,8%). Bone marrow infiltration was detected in 16 patients (30,2%)
and B symptoms were present in 52,8%. IPI score classified 13 cases
(24,5%) as lowrisk, 11 (20,8%) lowintermediate, 17 (32,1%) high
intermediate, and 12 (22,6%) as highrisk. After first line treatment,
complete remission (CR) was achieved in 64,2% of patients. CR rate
was 71% in patients with normal RDW and 59% in those with elevated
RDW, but this difference was not significant (p =0,53). Patients with a
high RDW value (>15%) at diagnosis showed a worse overall survival
(p =0,01; Figure 1a) and a worse progressionfree survival to first line
treatment (p =0,039; Figure 1b), when compared with those with a
normal RDW. Multivariate analysis confirmed the independent pre-
dictive value of RDW for overall survival.
This is one of several studies that shows that RDW value at
diagnosis constitute a simple, cheap and affordable prognostic factor
in DLBCL. What exactly RDW reflects in this disease (as well as in
other entities where its prognostic importance has been demon-
strated), from a pathophysiological point of view, requires a more in
depth investigation.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
339 |NEUTROPHIL/LYMPHOCYTE RATIO AND MONOCYTE/
LYMPHOCYTE RATIO PROMISING PROGNOSTIC BIOMARKERS
IN DIFFUSE LARGE BCELL LYMPHOMA?
C. Afonso
1
, S. Duarte
1
, B. Marques
1
, C. Barros Lima
1
, D. Neves
1
, A.
Lai
2
, M. J. Julião
2
, L. Ruzickova
1
, A. Roque
1
, J. P. Carda
1
, M. Gomes
1
,
A. Cipriano
2
, A. I. Espadana
1
1
Centro Hospitalar e Universitário de Coimbra, Clinical Hematology
Department, Coimbra, Portugal,
2
Centro Hospitalar e Universitário de
Coimbra, Pathology Department, Coimbra, Portugal
Background: During the past few years, several studies have tried to
identify biomarkers that could improve the current prognostic
assessment in diffuse large Bcell lymphoma (DLBCL). Neutrophil/
Lymphocyte Ratio (NLR) and Monocyte/ Lymphocyte Ratio (MLR) are
simple, costeffective and readily available tools that may have a
prognostic significance in DLBCL treated with RCHOP, according to
some studies.
Aims: To determine the prognostic value of NLR and MLR in DLBCL,
Not Otherwise Specified (NOS).
Methods: Retrospective analysis of 335 patients (pts) with newly
diagnosed DLBCL, NOS, between 2010 and 2019 in a tertiary centre;
only those treated with RCHOP(like) regimens were included. The
receiver operating characteristic curve (ROC) method was applied in
resetting the optimal cutoff point for predicting progression or
428
-
SUPPLEMENT ABSTRACTS
death from any cause. Variables with p <0.1 in univariate analysis
(UVA) were included in multivariate analysis (MVA).
Results: A total of 208 pts were identified. The median age at diag-
nosis was 63 years (2479), and 56% of pts were male. Stage III/IV
disease was present in 71% of pts, and B symptoms in 48%. Most pts
(78%) had extranodal involvement, and 51% presented lactate de-
hydrogenase (LDH) above the upper limit of normal (ULN). According
to the International Prognostic Index (IPI), 40% of pts were high
intermediate (HI) or high risk. The optimal cutoff value for NLR
was 3.09 (sensitivity 70.2% and specificity 50.4%; AUC 0.597,
p=0.019) and for MLR was 0.45 (sensitivity 64.3% and specificity
60.0%; AUC 0.624, p =0.003).
Higher NLR was significantly associated with Ann Arbor (AA) stage
III/IV (p =0.005), B symptoms (p =0.003), LDH>ULN (p <0.001),
and IPI HI/high risk (p <0.001). Similarly, a higher MLR was signifi-
cantly associated with higher incidence rate of B symptoms
(p <0.001) and LDH>ULN (P <0.001).
Considering the whole cohort, the 5year progressionfree survival
(PFS) was 59.2%, and the 5year overall survival (OS) was 68.9%. In
the UVA, age >65 (PFS, p =0.005, HR 1.85; OS, p <0.001, HR 2.73)
AA stage III/IV (PFS, p =0.001, HR 2.67; OS, p =0.003, HR 2.77), IPI
HI/high risk (PFS, p =0.005, HR 1.88; OS, p =0.004, HR 2.11),
LDH>ULN (PFS, p =0.010, HR 1.77; OS, p =0.043, HR 1.66), NLR
3.09 (PFS, p =0.003, HR 2.02; OS, p =0.010, HR 2.01) and
MLR0.45 (PFS, p =0.001, HR 2.08; OS, p =0.018, HR 1.83) were
significantly associated with shorter PFS and OS. However, in the
MVA, the NLR and MLR did not retain a statistically significant as-
sociation with PFS and OS.
Conclusions: In our cohort, elevated NLR and MLR were significantly
associated with several high risk clinical features, as well as poorer
outcome. However, their association with PFS and OS lost its sig-
nificance in MVA, suggesting that both ratios are not independent
prognostic factors in DLBCL pts undergoing treatment with RCHOP.
Therefore, the role of NLR and MLR in DLBCL may require further
validation before widespread clinical use.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
340 |RETROSPECTIVE APPLICATION OF THE CNSIPI TO A
POPULATION OF DLBCL PATIENTS TREATED WITH IT MTX
PROPHYLAXIS: A SINGLE CENTRE ANALYSIS.
C. Flynn
1
, M. McCarthy
1
, T. Harvey
1
, R. Flavin
2
, B. Dunne
2
, S. Sukor
1
,
C. Grant
1
1
St James's Hospital, Medical Oncology, Dublin, Ireland,
2
St James's
Hospital, Pathology, Dublin, Ireland
Introduction: Central nervous system (CNS) relapse in diffuse large
Bcell lymphoma (DLBCL) is associated with a poor prognosis, with
a median survival of four months. There was no reproducible model
to estimate CNS relapse risk until the “CNSIPI” was reported
(Schmitz et al. JCO 2016). This uses six criteria to categorise pa-
tients with DLBCL into low, intermediate, and high risk for CNS
relapse with rates of 0.6%, 3.4% and 10.2% respectively at two
years.
CNS prophylaxis is given to those felt to be at high risk of CNS
relapse, however evidence for its use in the rituximab era is limited.
Traditionally, intrathecal methotrexate (IT MTX) has been used as
CNS prophylaxis, with rationale extrapolated from acute lympho-
blastic leukaemia studies. Highdose intravenous methotrexate (HD
MTX) has emerged as an alternative prophylactic strategy, with some
data to suggest improved outcomes. However, some recent studies
have failed to show benefit of either intervention.
Methods: A retrospective analysis was carried out on oncology pa-
tients treated with IT MTX as CNS prophylaxis for DLBCL in St
James's Hospital over a 7year period (20132019). Double and
triplehit lymphomas were excluded. Baseline clinical and histo-
pathological data was recorded, and CNSIPI scores were retro-
spectively applied. Survival data was analysed by the KaplanMeier
method.
Results: 37 patients were included with a median followup of 48
months (r =387). Median age was 67 (r =3486) and 62% were
male. 4 patients (11%) were HIVpositive. 16 patients (43%) had GC
subtype and 19 (51%) had nonGC subtype disease. Most patients
were treated with RCHOP (54%) or REPOCH (43%) chemo-
therapy. 6 patients were CD5+. 84% had stage IIIIV disease, and
59.5% had an elevated LDH at diagnosis. When CNSIPI was
applied, 18 (48.6%), 14 (37.8%) and 5 patients (13.5%) were clas-
sified as high, intermediate, and low risk for CNS relapse
respectively.
94.6% (n =35) achieved complete response with an overall survival
(OS) of 86.4% and progressionfree survival of 81%. OS was 77.8%,
92.8% and 100% in the high, intermediate, and lowrisk groups
respectively. 1 of 37 patients (2.7%) developed CNS relapse.
When divided by CNSIPI, CNS relapse rate was 0% for low
and intermediaterisk groups, and 5.6% for highrisk patients
(p =0.149). Five patients (13.5%) developed significant toxicity with
IT MTX. Two patients developed subdural haematomas, two
developed severe back pain, and one developed a refractory
headache.
Conclusion: CNS relapse rate in this cohort is low, particularly for
low and intermediaterisk CNSIPI groups, which both had rates of
0%. This is in keeping with other studies which have demonstrated
lower CNS relapse rates in the rituximab era. More studies are
required to further elucidate risk factors for CNS relapse and to
establish the role of CNS prophylaxis in the rituximab era. This is
particularly important now there has been a shift towards HD MTX,
which has much higher rates of toxicity.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Prevention and
Cancer Interception
No conflicts of interests pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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429
341 |CLINICAL RISK SCORES IN DIFFUSE LARGE B CELL
LYMPHOMA IS THERE STILL ROOM FOR IMPROVEMENT?
D. S. Neves
1
, S. Duarte
1
, C. Afonso
1
, B. Marques
1
, C. B. Lima
1
, A. Lai
2
,
A. Roque
1
, L. Ruzickova
1
, J. Carda
1
, M. Gomes
1
, A. Cipriano
2
, A.
Espadana
1
1
Centro Hospitalar e Universitário de Coimbra, Clinical Hematology
Department, Coimbra, Portugal,
2
Centro Hospitalar e Universitário de
Coimbra, Pathology Department, Coimbra, Portugal
Introduction: Diffuse Large B Cell Lymphoma (DLBCL), the most
common nonHodgkin lymphoma, despite having a standard of care
treatment (RCHOP), has heterogeneous clinical and molecular fea-
tures. The widely used risk scores are based on clinical and
biochemical parameters, which can underestimate the impact of
genomic signatures. Recognizing the score with better discriminative
power might be important to better identify the highrisk group, for
whom RCHOP may be insufficient. We aim to compare the prog-
nostic efficacy of scores used in DLBCL: IPI (International Prognostic
Index), NCCNIPI and GELTAMOIPI.
Methods: Retrospective analysis of 335 HIV negative pts with newly
DLBCL, uniformly treated with RCHOP (like) between 20102019.
Pts treated with palliative intent were excluded. The discrimination
value for progressionfree survival (PFS) and overall survival (OS)
was performed using logrank statistics. Multivariate analysis
included variables statistically significant (pvalue <0.05) in univar-
iate analysis, not included in each score calculation. Stratified models
for each risk scores were compared using Akaike's information cri-
terion (AIC) and concordance index (Cindex).
Results: A total of 228 pts was eligible, mainly male (54%, n =123),
median age 64 years (2287). At diagnosis 69.3% (n =158) were
stage III/IV, 40.4% had 2 extranodal sites and 28.6% had bulky
disease (n =62/217).
PFS at 5 years for low (L), lowintermediate (LI), high
intermediate (HI), and highrisk (H) was 79.9/58.7/51.6/39.5% for
IPI (HR =1.5; p <0.001),74.7/70/55.3/28.6% for NCCNIPI
(HR =1.7; p <0.001) and 93.3/67.3/35/25.7% for GELTAMOIPI
(HR =1.9; p <0.001). After multivariate analysis, the scores
remained discriminant for PFS (HR =1.6; p =0.002; HR =1.7;
p=0.007; HR =1.7; p =0.001, respectively).
OS at 5 years for L, LI, HI, and H was 86/67.9/63.7/41.6% for IPI
(HR =1.6; p <0.001), 85.7/80/62/30.8% for NCCNIPI (HR =2.2;
p<0.001) and 93.3/76/44/37.5% for GELTAMOIPI (HR =2;
p<0.001).
For PFS, GELTAMOIPI has a substantial improvement in the
model fitness (AIC 633/950/951 for GELTAMOIPI, IPI and NCCN
IPI, respectively) and a slightly better discrimination between short
and long survival times (Cindex 0.6426/0.6378/0.6095) compared to
the other scores, that also have an acceptable discrimination capac-
ity. OS showed concordant results (AIC 480/733/725 respectively;
Cindex 0.6916/0.6543/0.6573).
Thus, for both PFS and OS, GELTAMOIPI cannot accurately
identify very highrisk pts.
Conclusions: Our results showed that GELTAMOIPI has only a
marginal performance advantage in discriminating risk groups, when
compared with IPI and NCCNIPI. However, none of them precisely
identify the highrisk DLBCL pts, which highlight the need to develop
new prognostic scoring systems with improved capacity of risk
stratification, providing the selection of those in need of novel
therapies.
Keywords: Diagnostic and Prognostic Biomarkers
No conflicts of interests pertinent to the abstract.
342 |DIFFUSE LARGE B CELL AND HIGHGRADE LYMPHOMAS:
THERAPEUTIC RESPONSE DESCRIPTIVE RETROSPECTIVE
UNICENTRIC ANALYSIS
C. L. Pedrosa
1
, B. Castro
1
, R. P. Peixeiro
1
, L. Regadas
1
, R. Coutinho
1
,
R. Cabral
1
, J. Coutinho
1
1
Centro Hospitalar Universitário do Porto, Clinical Hematology, Porto,
Portugal
Introduction: Relapse/refractoriness (R/R) in diffuse large B cell
(DLBCL) and high grade (HGL) lymphomas affects more than 1/3 of
the patients, constituting an unfavorable prognosis and therapeutic
challenge.
Methods: This singlecenter retrospective analysis aims to describe
the response to 1st line and salvage treatment of patients with
DLBCL and HGL diagnosed between 20152019.
Results: 125 patients were diagnosed. Of these, 58 did not undergo
curative chemoimmunotherapy (RChT) (median age 76 years;
ECOG 2 in 40%). We analyzed 67 patients; 55% men; median age
61 years (52% >60 years); ECOG 2 in 10%. 10% were HIV+. 81%
were DLBCL (NOS n =47), 13% HGL and 6% PTLD. 9% had pri-
mary extranodal involvement. The IPI score was calculated: low:
26%; low intermediate: 30%; high intermediate: 33%; high: 7%. The
RChT schemes were RCHOP (n =44), RCNOP (n =10), Rmini
CHOP (n =8), others (n =5). Dose adjustment /replacement of
anthracycline was performed in patients who were more than 60
yearsold, had high ECOG and/or comorbidities. 25% underwent
radiotherapy in the first line treatment. 67% achieved complete
response (CR). The rate of R/R was 44.8% (relapse n =10;
refractoriness n =20). The median time to relapse was 10.5
months. At diagnosis, these patients had an IPI 2 in 87%, bulky
disease in 50% and 73% were CD5+. The activated B cell subtype
was identified in 33%. Five were double/tripleexpressers. Two
doublehit lymphomas were identified. Twentyfour patients un-
derwent a second line treatment. Only 29% reached CR (RICE
n=3; RDHAP n =2; RBendamustine n =1; CVP n =1). Four
patients underwent autotransplantation. Eight received 3 thera-
peutic lines. The median followup was 19.3 months. The mortality
rate was 36% (52% of the total diagnosed). 71% died from disease
progression. The median overall survival of patients undergoing 1st
RChT was 39 months.
430
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SUPPLEMENT ABSTRACTS
Conclusion: Due to advanced age, comorbidities and/or high ECOG,
only 54% of patients with DLBCL and HGL were chosen for curative
RChT. Only 9 are alive with a followup time 18 months. The
studied patients presented characteristics, risk factors and unsatis-
factory responses to RChT in R/R, as described. Thus, we emphasize
the adjusted selection of treatment strategies as a way to improve
the prognosis.
EA previously submitted to regional or national meetings (up to
1000 attendees).
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive Bcell
nonHodgkin lymphoma, Chemotherapy
No conflicts of interests pertinent to the abstract.
343 |THE PRIMARY RESULTS OF THE EFFICACY OF UPFRONT
HIGHDOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL
TRANSPLANTATION FOR IV STAGE AND HIGHINTERMEDIATE/
HIGH IPI RISK GROUPS DLBCL
A. Koviazin
1
, L. Filatova
1
, I. Zyuzgin
1
, A. Artemyeva
2
, M. Motalkina
1
,
Y. Chudinovskikh
1
, S. Volchenkov
1
, I. Poliatskin
2
, E. Cherkasova
1
,
S. Shalaev
1
, I. Ishmatova
1
, A. Zverkova
1
, M. Ghanzin
1
, Y. Oleinik
1
,
D. Burda
2
, T. Semiglazova
3
1
NMRC of Oncology named after N.N.Petrov of MoH of Russia,
Department of Hematology and Chemotherapy with Intensive Care unit,
SaintPetersburg, Russian Federation,
2
NMRC of Oncology named after N.
N.Petrov of MoH of Russia, Department of Pathology, SaintPetersburg,
Russian Federation,
3
NMRC of Oncology named after N.N.Petrov of MoH
of Russia, Department of Innovative Methods in Therapeutic Oncology
and Rehabilitation, SaintPetersburg, Russian Federation
Introduction: Approximately 30% of patients(pts) with IPI 2 diffuse
large Bcell lymphoma (DLBCL) have relapsed after the frontline reg-
imens. Highdose chemotherapy (HDCT) with autologous hematopoi-
etic stem cell transplantation (autoHSCT) in the first remission can be
an effective option to decrease the relapse rate in these patients.
Methods: 108 pts, which fit the following criteria: DLBCL NOS, age
1865, stage IV, IPI 2, treated by x6 CHOP/EPOCH/HCVAD +R in
frontline from 01.01.2010 to 31.12.2019 at NMRC of Oncology
named after N.N.Petrov of MoH of Russia were retrospectively
analyzed.
If patients achieved a complete response (CR) or partial response
(PR) after frontline, they enrolled into upfront HDCT with autoHSCT
group (Group 1, n =38) or followup group (Group 2, n =70) based
on multidisciplinary team (MDT) decision. More than one extranodal
involvement (extra) had 78.9% (30/38) pts in Group 1 and 75.7% (53/
70) pts in Group 2. MYC and BCL2 coexpression were analyzed in
84% (32/38) pts samples in Group 1 and 65.7% (46/70) in Group 2
and were present (DEL) in 46.8% (15/32) pts samples in Group 1 and
28.2% (13/46) in Group 2.
A Fisher's exact test (Fisher's) with a twotailed pvalue was used to
determine the difference in relapse rate between Group 1 and Group
2. A McNemar test (McNemar) with Yates correction (Yates) was
used to determine the difference in responses in Group 1 after
upfront HDCT with autoHSCT.
Results: CR after induction was achieved in 61% (23/38) pts in Group
1. After HDCT with autoHSCT, the CR rate increased to 97% (37/
38) and continues for a median of 30 (756) months in 87% (33/38)
pts. It demonstrates the statistically significant difference McNe-
mar =11.27 (p 0.001) and with Yates =10.42 (p =0.002). Early
relapses (ER) were diagnosed in 6% (2/38) pts, late relapses (LR) in
6% (2/38) pts. HDCT associated mortality (infection) has occurred in
3% (1/38) pts.
Group 2 pts achieved CR in 81% (57/70) cases. CR continues for
median 38 (873) months in 67% (47/70) pts. Group 2 pts have 14%
(14/70) ER and 6% (4/70) LR. No treatmentrelated deaths occurred.
ER rate was higher in Group 2 (p =0.048). In Group 2 pts with ˃1
extra experienced more ER (Group 1 3.3% (1/30), Group 2 20.8%
(11/53), p =0.048). DEL was significant in terms of both ER (Group 1
6.6% (1/15), Group 2 38.4% (6/13), p =0.029) and all relapses
(AR) (Group 1 6.6% (1/15), Group 2 53.8% (7/13), p =0.011). The
ER rate in Group 2 was significantly higher if the combination of ˃1
extra and DEL were present (Group 1 9.1% (1/11), Group 2 60%
(6/10), p =0.0237).
Conclusions:
1. CR rate significantly increased in DLBCL NOS pts with stage
IV, IPI 2 treated by upfront HDCT with autoHSCT.
2. ER rate significantly decreases in DLBCL NOS with stage IV,
IPI 2 after upfront HDCT with autoHSCT pts if ˃1 extranodal site,
DEL, and combination of these factors are present; AR rate decreases
if pts only have DEL.
EA previously submitted to EHA 2021.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Stem Cell
Transplant
No conflicts of interests pertinent to the abstract.
344 |REAL WORLD APPLICATION OF RCHOP FOR DIFFUSE
LARGE BCELL LYMPHOMA (DLBCL) IN BELGIUM AND ITS
IMPACT ON SURVIVAL.
W. Daneels
1
, M. Rosskamp
2
, G. Macq
2
, E. Saadoon
1
, A. Degeyndt
2
, F.
Offner
1
, H. AntoinePoirel
2
1
Ghent University Hospital, Department of Hematology, Ghent, Belgium,
2
Belgian Cancer Registry, Research Department, Brussels, Belgium
Introduction: There is a growing interest for realworld population
studies to compare the results of randomized clinical trials in an
unselected population, including the elderly and patients with
comorbidities or other malignancies. We evaluated the patterns of
SUPPLEMENT ABSTRACTS
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431
care for DLBCL in Belgium including the use of RCHOP and radio-
therapy (RT).
Methods: Coded data of all adult (20 year) DLBCL diagnosed 2013
2015 (n =1,888) were obtained via the Belgian Cancer Registry. Vital
status was available until July 1
st
2019. Data was extracted from
pathology reports (IHC & FISH biomarkers) and oncological care
programs (performance status & staging). Chemotherapy, stem cell
transplantation and RT were inferred from health insurance data of
reimbursed treatments. An inhouse algorithm identified chemo-
therapy regimens (e.g. RCHOP/RDHAP), the number of cycles and
intervals, switches between regimens and refractoriness. Inherent
limitations apply due to treatment inference and some missing
prognostic markers.
Results: Systemic firstline treatment was started in 85%, decreasing
with age to only 46%. Treatments varied significantly by age.
Anthracycline based regimens were most frequently used (76%),
even in the elderly (45%). RCHOP was used in 1163/1596(73%) of
treated patients. We could not discriminate RCHOP from R
miniCHOP, the preferred regimen in the elderly.
Survival 2year OS of all patients was 63% with a clear influence of
age (3184%) and linked to firstline treatments: standard RCHOP
(85%), other anthracycline(66%), incomplete RCHOP (55%), non
anthracycline (44%), only RT (43%) and no chemo/RT (15%).
Standard RCHOP The median [IQR] cycle interval was 21 [2122]
days, consistent across age groups. The median [IQR] number of
cycles was 6 [47] up to the age of 89, except for the age group 2039
with 4 [26] cycles. In 14% of patients aged 8589, and 5 patients
aged >90, 6 cycles were given. In multivariable analyses for OS,
standard RCHOP was associated with a HR of 0,38 (0,300,48).
Incomplete RCHOP ±RT In 337/1163 cases (29%) <6 cycles (or <4 if
Ann Arbor =I) were given (<4 cycles in 195/337 and 45 in 142/337).
Reasons could not be determined but include early death, resistance,
local disease and part of extended and/or nonreimbursed regimens. In
40/337 a second line regimen was started. RT was applied after <4 and
45 cycles in 39 and 30 patients. 5year OS ranged between 2078%
(Fig. 1) with RT groups and primary refractory cases associated with
the highest and lowest OS respectively.
Conclusions: For DLBCL in the Belgian realworld setting, RCHOP21
is the primary firstline treatment and completing 6 cycles is achieved
in the majority of patients, including the elderly. In 29% of cases <6
cycles were given, but those receiving consolidative radiotherapy
maintained a favorable OS, confirming the curative potential of less
immunochemotherapy followed by radiotherapy in selected patients.
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive Bcell
nonHodgkin lymphoma, Combination Therapies
No conflicts of interests pertinent to the abstract.
345 |OUTCOMES OF DIFFUSE LARGE B CELL LYMPHOMA
PATIENTS TREATED IN A BRAZILIAN PUBLIC CANCER CENTER
A REAL WORLD EXPERIENCE OF 809 PATIENTS IN A 11 YEAR
PERIOD.
M. Bellesso
1
, J. Pereira
1
, L. Bassolli
1
, A. N. R. Abdo
1
, W. F. S. Junior
1
,
R. D. Velasques
1
, A. A. G. S. Brandão
1
, R. B. Melo
1
, L. A. P. C. Lage
1
,
F. V. R. Maciel
1
, H. Visnadi
1
, R. Shcolnik
1
, G. Duffles
1
, J. I. Beraldo
1
,
A. Duran
1
, I. C. Soares
2
, S. A. C. Siqueira
3
, V. Rocha
1
1
Instituto do Câncer do Estado de São Paulo, Hematology, São Paulo,
Brazil,
2
Instituto do Câncer do Estado de São Paulo, Pathology, São Paulo,
Brazil,
3
Hospital das Clínicas da Faculdade de Medicina da Universidade
de São Paulo, Pathology, São Paulo, Brazil
432
-
SUPPLEMENT ABSTRACTS
Introduction: Diffuse Large B cell Lymphoma (DLBCL) is a heterog-
enous disease. Factors based on clinical and simple laboratory pa-
rameters are known and widely used such as the Revised
International Prognostic Index (RIPI) and National Comprehensive
Cancer Network IPI (NCCNIPI). Thus, we aimed to report real
world experience of outcomes of DLBCL lymphoma patients treated
in a Brazilian public cancer institution and evaluate the prognostic
role of RIPI and NCCNIPI.
Methods: This is an unicenter registry study including DLBCL pa-
tients in a public tertiary cancer center in São Paulo city, Brazil.
Consecutive patients diagnosed from 01/2009 to 12/2020, aged
18 years, treated with RCHOP or RCHOP like regimens were
included. Patients with AIDS related lymphoma, or primary medi-
astinal lymphoma were excluded. Patients were stratified by RIPI
and NCCNIPI. Progression free survival (PFS) and overall survival
(OS) were estimated by KaplanMeier curve. All variables studied
showed less than 10% of missing data and valid percent were
reported.
Results: We analyzed 809 patients who met the eligibility criteria.
416 (51.5%) were males. Median age was 59.9 (IQR 44.9 68.2)
years, 271 (31.3%) presented ECOG 2, 561 (74.9%) advanced
disease, 695 (87.4%) elevated LDH and 638 (82.2%) extranodal
involvement. Patients were classified according to prognostic
scores, 411 (50.8%) were considered poor prognosis by RIPI (3 pts)
and 465 (57.5%) were classified as high risk or highintermediate
NCCNIPI (4 pts).
Response status after first line treatment was available in 678 pa-
tients, 456 (67.2%) achieved CR. Median followup 4.6 95CI (4.2
5.0) years.
Estimate 4 year OS and PFS for the entire patient cohort were 65.3%
and 60.4%, respectively.
Patients identified as very good (0), good (12) and poor (3)prog-
nosis by RIPI presented 4year OS 94%, 75.2% and 52.8%, p <
0.0001, and 4years PFS was: 94%, 68.8%, 48.2%, respectively, p <
0.001. (Figure)
Estimate 4 year OS and PFS according to NCCNIPI: low (01), low
intermediate (23), highintermediate (45) and high risk were
respectively 95.5%, 75.4%, 60.3%, 35.9%, p <0.0001) and 93.7%,
69.7%, 54.7% and 33.3%, p <0.001, respectively. (Figure).
Conclusion: In this large cohort of DLBCL patients diagnosed and
treated in a public University center in Brazil, we have observed a
higher frequency of patients with unfavorable prognosis 57.5%
SUPPLEMENT ABSTRACTS
-
433
NCCNIPI (4 pts) and 50.8% RIPI (3 pts) when compared to data
published in the literature 39% and 45%, respectively. OS and PFS
are comparable to data of literature according to NCCNIPI and RIPI
scores. Both scores discriminate groups of patients with DLBCL in a
middleincome country and may be used to study further strategies
to improve outcomes of patients with poor prognosis.
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
346 |TREATMENT AND OUTCOMES OF PATIENTS WITH
POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER: A
SINGLE CENTRE EXPERIENCE
C. de Ramon Ortiz
1
, K. Samii
1
, K. Hadaya
2
, A. Avram
3
, Y. Beauverd
1
1
Geneva University Hospitals, Haematology Division, Department of
Oncology, Geneva, Switzerland,
2
Geneva University Hospitals, Nephrology
Division, Department of Medicine, Geneva, Switzerland,
3
Geneva
University Hospitals, Pathology Division, Department of Genetics and
Laboratory Medicine, Geneva, Switzerland
Background: Posttransplant lymphoproliferative disorder (PTLD) is
a potentially severe complication that takes place after solid (SOT)
or allogeneic hematopoietic stem cell transplant (HSCT). To
date, its treatment is not standardised, and choice of therapy de-
pends on histology and clinical presentation. We report the results
of a 10 years (yrs) singlecentre retrospective study assessing
presentation, treatment patterns and outcomes of patients with
PTLD.
Methods: Patients 18 yrs diagnosed with a PTLD between 2011
and 2020 were identified in our medical records database. Primary
endpoints were 2 yrs progressionfree survival (PFS), overall sur-
vival (OS), and relapse incidence (RI) estimated with KaplanMeier
and comparison between HSCT and SOT group. Secondary end-
points were the overall response rate (ORR) and complete
response rate (CRR) at the end of first line treatment. Exploratory
univariate analysis for OS, PFS were investigated using Cox
regression model.
Results: A total of 38 patients were included. Patient's characteristics
and treatment strategies are presented in Table 1. HCST patients
present a significantly higher prevalence of early onset PTLD (90% in
HCST group vs 0% in SOT group), positive EBER immunostaining
(100% vs 22%) and detectable Epstein Bar Virus (EBV) viremia (100%
vs 28%), higher LDH (95% vs 66%), IPI score 35 (50% vs 33%), with a
remarkable higher use of single agent Rituximab as first line therapy
in HSCT patients (65% vs 11%). 2 yrs PFS was 54% (95%CI 3673%)
for the entire cohort, 42% (95%CI 1667%) for HSCT and 67% (95%
CI 4192) for SOT; pvalue 0.23. 2 yrs OS was 53% (95%CI 4166%)
for the entire cohort, 42% (95% CI 1667%) for HSCT and 65% (95%
CI 3991) for SOT; pvalue 0.22. 2 yrs RI was 9% (95% CI: 021%) for
the entire cohort, 0% for HSCT and 14% (95% CI 033%) for SOT; p
value 0.26. ORR and CRR were similar with 82% (75% for HSCT, 89%
for SOT, pvalue 0.41) at the end of first line treatment. High IPI
score (35) demonstrated worse outcome for PFS (HR: 2.5, 95%CI
0.956.65, pvalue 0.063) and OS (HR: 2.4, 95%CI 0.926.48, pvalue
0.07). A total of 17 patients died during followup: 7 during first line
treatment of PTLD complication and multiorgan failure (5 in the
HSCT group, 2 in the SOT group; pvalue 0.41); 2 following PTLD
relapse after first CR (0 in the HSCT group, 2 in the SOT group;
pvalue 0.22).
TABLE 1Patient's baseline characteristics and first line
therapy
434
-
SUPPLEMENT ABSTRACTS
Conclusion: This study highlights the clinical and therapeutic het-
erogeneity of PTLD. We observe a worse 2 yrs PFS and OS in patients
with high IPI score. CRR after first line treatment is almost 90% in the
SOT group, with a 2 yrs OS of 53%, consistent with previous studies
(Trappe et al, JCO 2017). The higher mortality observed in the HSCT
group suggests that serious treatmentrelated toxicities remain main
challenges in this fragile patient population. New tools to guide
therapeutic approaches in PTLD patients are warranted.
Keywords: Lymphoid Cancers Other
No conflicts of interests pertinent to the abstract.
347 |DOUBLEHIT (DHL) AND TRIPLEHIT LYMPHOMAS (THL):
REAL LIFE EXPERIENCE OF 46 CONSECUTIVE PATIENTS FROM A
SINGLE INSTITUTION IN SPAIN
E. M. Gonzalez Barca
1
, J. M. Sancho
2
, J. Rovira
3
, N. Kelleher
4
,
M. Kara
1
, M. Encuentra
1
, E. Domingo Domenech
1
, A. C. Oliveira
1
,
J. M. Ribera
2
, L. Escoda
3
, A. Sureda
1
1
Institut Català d'Oncologia, Hospital Duran i Reynals, Institut
d'Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de Barcelona,
Hematology, L'Hospitalet de Llobregat, Barcelona., Spain,
2
Institut Català
d'Oncologia, Hospital Germans Trias i Pujol, Institut de Recerca contra la
Leucèmia Josep Carreras, Universitat Autònoma de Barcelona, Badalona,
Hematology, Barcelona, Spain,
3
Institut Català d'Oncologia, Hospital
Universitari Joan XXIII, Hematology, Tarragona, Spain,
4
Institut Català
d'Oncologia, Institut d'Investigació Biomèdica de Girona (IDIBGI),
Universitat de Girona, Hematology, Girona, Spain
Introduction: Doublehit (DHL) and triplehit lymphomas (THL) have
been described in the 2016 revised WHO classification, they repre-
sent a new entity called highgrade Bcell lymphoma (HGBCL) with
rearrangements of MYC and BCL2 and/or BCL6. DHL/THL have been
described as clinically aggressive with a high risk of central nervous
system (CNS) and extranodal organ involvement and with a worse
prognosis when treated with standard RCHOP.
Patients and Methods: Retrospective study of 46 consecutive pa-
tients with HGBCL with DHL/THL, diagnosed from March 2015 to
November 2020, in centers of the Catalan Institute of Oncology in
Spain. Survival curves were plotted by the KaplanMeier method.
Comparison analysis for survival was performed with the logrank
test.
Results: Clinical characteristics at diagnosis are shown in the table.
Of note, 98% presented extranodal disease: bone marrow (n =11),
bone (n =11), kidney/adrenal (n =10), lung (n =9), gastrointestinal
(n =8), soft tissue (n =8), and CNS involvement (n =2). Three pa-
tients did not receive first line treatment (2 due to old age and 1
patient died few days after diagnosis). Among the 43 patients
treated, regimens used were: RCHOP: 22 (51%) patients (2 of them
RminiCHOP), DAEPOCHR: 14 (33%), intensive regimen used in
Burkitt lymphoma: 4 (9%), RGEMOX: 1 patient, radiotherapy:1 pa-
tient, unknown:1. CNS treatment or prophylaxis consisted in high
dose intravenous methotrexate in 9 patients, and intrathecal meth-
otrexate in 5. No patient received stemcell transplant in first line.
Overall response was 67%; complete remission (CR): 23 (53%), par-
tial remission (PR): 6 (14%), progression: 12 (28%) and 2 patients
were not evaluable. CR was 45% after RCHOP vs 67% with inten-
sive regimens. With a median followup for the alive patients of 41
months, 23 (50%) patients died, 18 (39%) due to progressive lym-
phoma, 3 due to septic shock, 1 gastric carcinoma and 1 severe
bronchiolitis. There were not CNS relapses. Progressionfree survival
(PFS) and overall survival (OS) at 3 years of the 46 patients were 42%
(95% CI 2657) and 47% (95% CI 3862), respectively. PFS at 3 years
FIGURE 1 Survival curves for PFS and OS
SUPPLEMENT ABSTRACTS
-
435
of patients treated with RCHOP versus patients treated with
intensive regimens was 40% (95% CI 1763) versus 51% (95%CI 25
77), and OS at 3 years was 47% (95%CI 2469) versus 56% (95%CI
2983), without statistical significant differences.
Conclusions: Almost all patients with HGBCL DHL/THL have extra-
nodal involvement at diagnosis and have other factors of poor
prognosis as previously described. Survival of the whole series is
poor. Nevertheless, although this is a small series, our data suggest
that higher therapeutic intensity could improve outcomes, but PFS
and OS of patients treated with RCHOP are better than in other
older retrospective studies. Therefore, a prospective randomized trial
is mandatory to clarify the role of intensive treatments in these pa-
tients.
FIGURE 1: Progression free survival of patients with high grade
lymphoma double.triple hit according to the first line of treatment
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
348 |PRIMARY ORAL CAVITY LYMPHOMAS (POCL).
FEATURES OF 67 PATIENTS TREATED AT A SINGLE INSTITUTION
IN ARGENTINA
A. C. Jozami
1
, J. Arriola
1
, M. Marquez
1
, P. Luchetta
1
, I. Annetta
1
, N.
Diaz Velez
1
, V. Courreges
1
1
Oncology Hospital Maria Curie, Hematology, Buenos Aires, Argentina
Introduction: POCL represents 28% of head and neck cancers. They
are characterized by their locoregional growth, low specificity of the
initial symptoms, and a predominance of aggressive histology.
Objective: To describe the characteristics of 67 patients with POCL.
Methods: the medical records and pathological anatomy studies of
patients admitted to the Hematology and Stomatology Services be-
tween the years 1996 and 2020 were evaluated.
Results: Ages: 19 to 88 years old, mean: 52; Masc. 44 and, Fem. 23.
436
-
SUPPLEMENT ABSTRACTS
Locations: lower jaw: 45% upper jaw 27%, base of tongue 13%, hard
palate 11%, floor of mouth 4%.
Histology: diffuse large Bcell lymphoma (DLBCL): 52%, plasma-
blastic lymhoma (PBL): 24%, Follicular L 10%; PTCL NOS 7%; Burkitt
2%, NK/Tcell L: 1,5%; MALT: 1,5%.
Stages: I: 66%, II: 25% IV: 9%, due to bone marrow infiltration
Increased LDH was observed in 33% of patients, β‐2microglobulin in
23%, and erythrocyte sedimentation in 23%.
Toxic antecedents: tobacco 30% and dental prostheses in 15%.
The initial symptoms were mobility and pain of the teeth, a rapidly
growing painful tumor in the jugal mucosa, and torpid oral ulcers.
HIV positive in 16 patients, 13 with PBL and 7 with DLBCL.
Treatment: it was carried out according to the histology, the patient's
PS, viral status and date of diagnosis.
The following regimes were used: CHOP, RCHOP, CVP; RCVP,
CAVPE, CNOP; DAEPOCH. In 15 patients there are no data on the
treatment carried out. 6 cases received local radiotherapy. CNS
prophylaxis with systemic methotrexate or intrathecal drugs was
performed according to the schedule chosen and the patient's risk
factors.
Responses: complete remission (CR) in 37%, partial remission (PR) in
16% of those who underwent treatment. There's no data in 22 pa-
tients due to loss of followup.
Followup time ranged from 1 year to 21 years.
Conclusions: In this series of patients, we observed most aggressive
histology, with fast growing locoregional tumors. Dental alterations
led to consultations with stomatologists, who took diagnostic bi-
opsies. There was a predominance of males, of B lineage, with middle
ages predominate. The IPI and the stage were not useful tools for the
evaluation of this pathology.
The association with HIV was observed in 28% of the cases, the
majority were PBL (68%), with increased DLBCL histology.
Favorable responses were observed, with prolonged survival in cases
with less aggressive histology.
Keywords: Extranodal nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
349 |LONG TERM OUTCOMES OF EARLY STAGE PRIMARY
GASTRIC DIFFUSE LARGE BCELL LYMPHOMA: A MULTICENTRE
RETROSPECTIVE STUDY
C. D. Smith
1
, Y. S. Chin
2
, S. A. Gupta
3
, S. R. Thompson
1
1
Prince of Wales Hospital, Department of Radiation Oncology, Randwick,
Australia,
2
St George Hospital, Department of Radiation Oncology,
Kogarah, Australia,
3
Calvary Mater Hospital, Department of Radiation
Oncology, Newcastle, Australia
Introduction: Early stage gastric disease is an uncommon sole
manifestation of diffuse large Bcell lymphoma (DLBCL). Radio-
therapy (RT) can be used as part of a combined modality approach
in the treatment of early stage nodal DLBCL with excellent results.
In primary gastric DLBCL (PGDLBCL) the role of RT is not well
established and outcome data are lacking. We assessed the long
term outcomes of patients who received RT as part of their
curativeintent treatment for early stage PGDLBCL at three NSW
institutions.
Methods: We carried out a retrospective, multicentre study of pa-
tients with PGDLBCL who had had treatment with radiotherapy
between 01/03/1999 and 29/05/2020. Eligible patients were age
18 years, received radiotherapy as part of combined modality
therapy, pathological diagnosis of DLBCL, Lugano stage III. Timeto
event outcomes were calculated from day 1 of treatment. Toxicities
were extracted from the medical chart per CTCAE v4.0
Results: There were 14 eligible patients. Median age was 75 years
(range 48 84). 10 (71%) patients had Lugano stage I disease, 4
(29%) had stage II. IPI at diagnosis was 0 in 14%, 1 in 57% and 2 in
29%. All patients previously received systemic therapy (11 RCHOP,
1 CHOP, 2 other). 5 (33.3%) patients were H pylori positive and all 5
received H Pylori eradication prior to treatment. Median prescribed
RT dose was 30.6Gy (range 30 45) in 17.5 fractions (range 15 25).
10 (71%) treatments were delivered with 3D conformal technique, 4
(29%) with VMAT.
Thirteen patients had disease assessed prior to consolidation
RT: 10 (77%) achieved complete response, and 3 (23%) partial
response. During median follow up of 56 months (IQR 2970),
estimated 5 year local relapse free survival (LRFS), distant relapse
free survival (DRFS), and progression free survival (PFS) were 100%,
93% (95%CI; 80.3100), and 93% (95%CI; 80.3100), respectively.
There was 1 documented recurrence which was out of RT field. 5
year OS was 93% (95%CI; 80.3100). There were no acute grade 3
5 radiotherapy toxicities. There was one grade 3 late toxicity; a
stricture requiring feeding tube. No treatment related deaths
occurred.
Conclusions: Combined modality treatment with radiotherapy for
early stage PGDLBCL has excellent local control and survival out-
comes. In our small series PGDLBCL appeared to have superior
outcomes when compared to nodal DLBCL. Treatment is well toler-
ated with modest toxicity.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Extranodal
nonHodgkin lymphoma, Radiation Therapy
No conflicts of interests pertinent to the abstract.
350 |DIFFUSE LARGE BCELL LYMPHOMA IN ELDERLY
PATIENTS: OUTCOME IN REALWORLD CLINICAL PRACTICE
B. Marques
1
, S. Duarte
1
, C. Afonso
1
, C. B. Lima
1
, D. Neves
1
, A. C. Lai
2
,
M. J. Julião
2
, A. Roque
1
, L. Ruzickova
1
, J.P. Carda
1
, M. Gomes
1
, A.
Cipriano
2
, A. I. Espadana
1
1
Centro Hospitalar e Universitário de Coimbra, Clinical Hematology
Department, Coimbra, Portugal,
2
Centro Hospitalar e Universitário de
Coimbra, Pathology Department, Coimbra, Portugal
SUPPLEMENT ABSTRACTS
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437
Introduction: Diffuse large B cell lymphoma (DLBCL) is the most
common type of nonHodgkin lymphoma, and is more frequent in
elderly patients (pts), which have a worse prognosis than younger
patients. This is partially explained by the existence of comorbidities
and poor performance and functional status, limiting the use of R
CHOP as standard therapy. We aim to evaluate the impact of clin-
ical factors in therapeutic decisions and outcomes of elderly DLBCL
pts.
Methods: Retrospective analysis of >65 years pts with DLBCL, NOS
diagnosed in our center, between 20102019. Pts were divided in 2
groups: 66–79 years (elderlyE) and 80 years (very elderlyVE). Pts
baseline characteristics, treatment and outcomes were collected.
Multivariate analyses were performed by stepwise variable selection,
with P<0.1 in univariate analysis.
Results: We identified 193 pts, 127 (65.8%) in E group, and 66
(34.2%) in VE group. At diagnosis, 21.0% of E group and 68.8% of VE
group had an ECOGPS2 (P<0.001). The VE pts presented more
frequently with high risk IPI (22.2% vs 47.3%, P=0.006), as well as
NCCNIPI and GELTAMOIPI. Proportions of pts with bulky mass
(P=0.911) and germinal center Bcell subtype (P=0.81) were similar
in both groups.
E group received curative intent immunochemotherapy (ICT) in
92.1% (n =117) and VE in only 53% (n =35) (P<0.001). Elderly pts
were more likely to receive rituximab (87.2 % vs 41.3%, P<0.001) and
anthracycline (88.2% vs 47.0%; P<0.001) than VE. Among pts with
curative intent ICT, complete response rate was 57.5% vs 25.8%
(P<0.001). Palliative therapy in E (n =10) and VE (n =30) groups
included steroids (70.0% vs 70.0%), PEPC regimen (0% vs 6.7%) or no
treatment at all (30.0% vs 23.3%). There were 14 pts (11.1%) in E group
and 6 pts (9.3%) in VE group who received consolidation radiotherapy
(RT). One patient (1.5%) in VE group received palliative RT.
The median followup was 7.1(5.37.2) years. Elderly pts pre-
sented a significantly better PFS than VE (3.3[0.75.9] vs 0.8[0.60.9]
years, HR 1.9 [CI95% 1.42.8], P<0.001) and OS (4.5[1.67.4] vs 0.9
[0.41.3] years, HR 2.2 [CI95% 1.53.2], P<0.001).
Overall, pts who received curative intent ICT presented a
longer OS (3.3 vs 0.4 years, HR 3.3 [CI95% 2.25.0], P<0.001) and
PFS (2.3 vs 0.2 years, HR 3.0 [CI95% 2.04.3], P<0.001). In multi-
variate analysis, female sex, stage I/II, absence of bulky mass and
treatment with rituximab predicted a favorable prognosis in E group
for PFS and OS. In VE pts, only female sex, ECOGPS 01 and
treatment with rituximab remained independent favorable prog-
nostic factors.
Conclusions: In our cohort, VE pts presented with a poorer functional
status and a higher risk disease, when compared to E pts. PFS and OS
was improved with curative intent ICT in both age groups, indicating
that this treatment should be considered, even in the oldest patients,
after a careful evaluation of ECOGPS and comorbidities.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemo-
therapy, Immunotherapy
No conflicts of interests pertinent to the abstract.
351 |RITUXIMAB AND NONPEGYLATED LIPOSOMIAL
DOXORUBINCIN (RNPLD) TREATMENT IN PATIENTS 80 YEARS
OF AGE OR OLDER AFFECTED BY DIFFUSE LARGE B CELL
LYMPHOMA (DLBCL): A 2020 UPDATE AND IMPLICATIONS OF
CLINICAL AND PATHOLOGICAL FACTORS
C. Cantò
1
, E. Pennese
1
, M. Di Nicola
2
, G. Ricciuti
3
, F. Restuccia
1
, S.
Luciani
1
, F. Angrilli
1
1
Civic Hospital “Santo Spirito” Pescara, Center for the Diagnosis and
Treatment of Lymphomas, Department of Oncology and Hematology,
Pescara, Italy,
2
“G. d'Annunzio” University, Department of Medical, Oral
and Biotechnological Sciences, Chieti, Italy,
3
IRCCS “Casa Sollievo della
Sofferenza”, Department of Hematology, San Giovanni Rotondo (FG), Italy
Background: In 2018 we report a rituximab plus nonpegylated lip-
osomial doxorubicin (RNPLD) combination for patients 80 years or
older with diffuse B cell lymphoma (DLBCL) or grade 3 b follicular
lymphoma. The overall 3year survival, causespecific survival and
progressionfree survival rates were 46%, 55%, and 44%, respectively.
According to these results, RNPLD has become the new standard
treatment in patients 80 years old with aggressive B lymphoma, in our
institution. To better investigate the prognostic role of clinical and
pathological factors, we analyzed the same immunochemotherapy
combination in a larger cohort of patient 80 years or older with DLBCL.
Methods: We retrospectively and prospectively analyzed data of pa-
tients 80 years or older with untreated histologicallyproven CD20
positive DLBCL, Ann Arbor stage I to IV from our institution. Pa-
tients received a combination treatment with rituximab plus non-
pegylated liposomial doxorubicin. The regimen consisted of R 375 mg/
sqm and NPLD 50 mg/sqm administered intravenously on cycle day 1,
plus prednisone 50 mg orally on days 1 to 5, every 21 days for 6
courses.
Results: Between May 2010 and April 2019, we enrolled 50 patients
(median age 84, range 8096, M/F:27/23). The median followup time
was 28 months (range 10104). The overall 3years survival, cause
specific survival, and disease free survival rates were 49.9±7.6%,
55.5±7.9%, and 48.5±7.8%, respectively. Treatment was well toler-
ated with only mild toxicities, without treatment related hospitaliza-
tion or toxic deaths. Patients achieving EFS12 and EFS18 had an
overall3years survival of 66±13.0% and 67.9±7.0%, respectively.
Conclusion: Our results confirm that, in patients 80 years or older
with DLBCL, RNPDL is very effective and safe combination. Among
prognostic factors, only the elevated LDH (1.25 upper limit)
strongly correlates with overall survival and risk of relapse, in uni-
variate (p =0.001, p =0.003) and multivariate (p =0.002, p =0.005)
analysis, respectively. In patients who achieved EFS18 the probability
to survive 24 and 36 months is of 90.5 and 67.9%, respectively. This
analysis suggests that EFS18 will be useful in patient counseling and
should be considered as a robust end point for future studies ofnewly
diagnosed very elderly DLBCL patients.
Keywords: Aggressive Bcell nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
438
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SUPPLEMENT ABSTRACTS
HODGKIN LYMPHOMA
352 |BRENTUXIMAB VEDOTIN CONSOLIDATION AFTER
AUTOLOGOUS STEM CELLS TRANSPLANTATION FOR HODGKIN
LYMPHOMA: A REALLIFE EXPERIENCE BY FONDAZIONE
ITALIANA LINFOMI (FIL)
F. Massaro
1
, V. Pavone
2
, P. M. Stefani
3
, B. Botto
4
, A. Pulsoni
5
, C.
Patti
6
, M. Cantonetti
7
, A. Visentin
8
, P. R. Scalzulli
9
, A. Rossi
10
, S.
Galimberti
11
, M. Cimminiello
12
, G. Gini
13
, M. Musso
14
, M. Sorio
15
, A.
Arcari
16
, V. R. Zilioli
17
, A. Bari
18
, D. Mannina
19
, A. Fabbri
20
, G.
Pietrantuono
21
, O. Annibali
22
, A. Tafuri
23
, E. Prete
2
, A. Mulè
6
, E.
Barbolini
24
, L. Marcheselli
25
, S. Luminari
26
, F. Merli
26
1
PhD Program in Clinical and Experimental Medicine, University
of Modena and Reggio Emilia, Modena, Italy,
2
Department of
Hematology and Bone Marrow Transplant, Hospital Card. G. Panico,
Tricase, Italy,
3
Hematology Unit, General Hospital Ca' Foncello,
Treviso, Italy
4
Division of Hematology, Città della Salute e della Scienza
Hospital and University, Turin, Italy,
5
Hematology Unit, Department of
Translational and Precision Medicine, Sapienza University, Rome, Italy,
6
Division of Hematology, Azienda Villa SofiaCervello, Palermo, Italy,
7
Unit of Lymphoproliferative Disorders, Policlinico Tor Vergata,
Rome, Italy
8
Hematology and Clinical Immunology Unit, Department of
Medicine (DIMED), University of Padua, Padua, Italy,
9
Department of
Hematology, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy,
10
Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII,
Bergamo, Italy,
11
Division of Hematology, Department of Clinical and
Experimental Medicine, University of Pisa, Pisa, Italy,
12
Hematology, San
Carlo Hospital, Potenza, Italy,
13
Division of Hematology, Azienda
Ospedaliera Universitaria Ospedali Riuniti, Ancona, Italy,
14
Department
of Oncology, Hematology and BMT Unit, Casa di Cura La Maddalena,
Palermo, Italy,
15
Department of Clinical and Experimental Medicine,
Hematology and Bone Marrow Transplant Unit, Verona, Italy,
16
Hema-
tology Unit, Ospedale Guglielmo da Saliceto, Piacenza, Italy,
17
Division
of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan,
Italy,
18
Dipartimento di Scienze Mediche e Chirurgiche MaternoInfantili
e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italy
19
Unit
of Haematology, Azienda Ospedaliera Papardo, Messina, Italy,
20
Hema-
tology Unit, Azienda OspedalieroUniversitaria Senese, Siena, Italy,
21
Hematology and Stem Cell Transplantation Unit, IRCCS Centro di
Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy,
22
Unit
of Haematology and Stem Cell Transplantation, Campus BioMedico
University, Rome, Italy,
23
University Hospital Sant'Andrea, Sapienza,
University of Rome, Rome, Italy,
24
Gruppo Amici dell'Ematologia GRADE,
Onlus Foundation, Reggio Emilia, Italy,
25
Fondazione Italiana Linfomi,
Onlus, Modena, Italy,
26
Hematology Unit, Azienda Unità Sanitaria Locale
IRCCS, Reggio Emilia, Italy
Introduction: Classical Hodgkin lymphoma (cHL) is a highly curable
cancer, but up to 30% of patients have a refractory or relapsed (R/R)
disease. Salvage therapy followed by consolidation with autologous
hematopoietic stem cell transplantation (ASCT) can save only
approximately half of R/R patients.
In the phase 3 AETHERA trial, cHL patients at highrisk of pro-
gression or relapse who received Brentuximab Vedotin (BV) as
consolidation therapy after ASCT showed a reduced risk of pro-
gression compared to a placebo group, with 5year progressionfree
survival (PFS) rates of 59% and 41%, respectively. We report here
the results of a reallife study on 105 cHL patients treated with BV as
consolidation after ASCT.
Methods: This retrospective study included R/R cHL patients from
15 Italian centers treated between April 2011 and August 2020.
Patients were eligible if they had received at least 2 cycles of BV
after ASCT, independently from prior treatments. The primary aim
was PFS and OS assessment and its comparison to data already re-
ported in literature.
Results: We included 105 patients, with a median followup of 20
months (range 2108). Patients received a median of 2 lines of
treatment before ASCT. The 51% (54 patients) of total population
received BV also immediately before ASCT. PETCT evaluation
before and after ASCT reported a Deauville score (DS) 13 in
72 (75%) and 68 (78%) patients, respectively. Considering pre ASCT
highrisk features (refractory disease, CR <12 months, extranodal
disease at relapse), 30 (29%) patients presented at least 2 factors.
The median number of BV consolidation cycles was 10. A com-
plete schedule of sixteen cycles of BV was administered to 57 (54%)
subjects in the whole population (60% of patients who received both
consolidation and pre ASCT and 43% of subjects treated with BV
postASCT only). Main causes for treatment interruption were:
adverse events (AEs; 15; 33%), disease progression (13; 28%),
consolidation with alloSCT (8; 17%). Among the grade 34 AEs
leading to treatment interruption, we reported 8 peripheral neu-
ropathies, 4 infections, 2 infusion reactions, 1 liver toxicity.
Concerning efficacy data, the 3year PFS and OS were 62%
(95% CI: 4972) and 86% (95% CI: 7393), respectively (Figure 1).
In univariate analysis the only feature significantly associated with
both reduced PFS and OS was a DS 45 before ASCT (HR 3.81; 95% CI:
1.808.09; p <0.001). Interestingly the administration of BV pre ASCT
was not associated with different risk of progression PFS (HR 0.87,
95% CI 0.441.73, p =0.965) or death (HR 0.71, 95% CI 0.202.49,
p=0.594).
Conclusions: BV treatment as post ASCT consolidation is confirmed by
our reallife study as an effective and safe option for R/R cHL patients
in line with the results of the AETHERA trial. The use of BV also before
ASCT did not negatively impact on its safety and efficacy, and likely
allowed to offer to a higher number of patients the option of ASCT.
Keywords: Hodgkin lymphoma, Immunotherapy
Conflicts of interests pertinent to the abstract
A. Pulsoni
Consultant or advisory role: Takeda
M. Cantonetti
Consultant or advisory role: Takeda
SUPPLEMENT ABSTRACTS
-
439
Educational grants: Takeda
A. Visentin
Educational grants: Takeda
A. Rossi
Consultant or advisory role: Takeda
V. R. Zilioli
Consultant or advisory role: Takeda
A. Fabbri
Consultant or advisory role: Takeda
Educational grants: Takeda
F. Merli
Consultant or advisory role: Takeda
353 |BRENTUXIMAB VEDOTIN PLUS BENDAMUSTINE AS
FIRST SALVAGE TREATMENT IN PATIENTS WITH RELAPSED OR
REFRACTORY HODGKIN LYMPHOMA. EXPERIENCE AT
DONOSTIA UNIVERSITY HOSPITAL, SPAIN
B. Mendibil Esquisabel
1
, L. Ondarra Segurola
1
, A. Altuna Mongelos
1
,
J. Iriondo Alzola
1
, A. Zumalde Murua
1
, A. Arambarri Oyarzabal
1
,
N. F. Rois Pego
1
, I. Zeberio Etxetxipia
1
1
Hospital Universitario Donostia, Hematology Department, Donostia,
Spain
Introduction: Hodgkin lymphoma (HL) is a highly curable disease
with frontline treatment. Nonetheless, up to 30% of the patients are
primarily refractory or experience relapse after upfront chemo-
therapy. Salvage chemotherapy followed by autologous stem cell
transplantation (ASCT) is the standard of care in these patients.
Achieving complete response (CR) prior to ASCT is one of the
strongest predictors of favorable outcome after ASCT. Although
Brentuximab vedotin (BV) can only be used in patients with relapsed
or refractory HL who have received at least two prior salvage
treatments, studies have shown that the combination of BV and
bendamustine as first salvage therapy is highly active in this patient
population, increasing the number of patients who achieve CR prior
to ASCT
1
. We hereby report the results of patients treated with BV
and bendamustine as first salvage regimen (out of label) in our
center.
Methods: We conducted a retrospective analysis of 12 patients un-
der 60 years with relapsed or refractory HL who received BV and
bedamustine as first salvage regimen.
Results: Patient characteristics are shown in Table 1. A total of 12
patients (6 primary refractory and 6 relapsed) received 3 or 4 cycles
of BV plus bendamustine as first salvage regimen. Overall, 11/12
patients achieved a response and 1 patient who had been primary
refractory progressed during treatment. Nine patients obtained a CR,
including all relapsed patients and three of the primary refractory,
and two achieved partial response (PR), both being primary re-
fractory. All patients who obtained a response underwent ASCT and
100% of the patients achieved CR at day +100 after ASCT. Three
FIGURE 1 KaplanMeier plots showing OS and PFS
440
-
SUPPLEMENT ABSTRACTS
of the twelve patients presented high risk characteristics for
relapse after ASCT and received maintenance BV. With a median
followup time of 23 months from ASCT 3 patients have relapsed at
4, 8 and 22 months, none of them having received maintenance
therapy.
No serious adverse events were observed. A total of 7 patients
experienced infusionrelated reactions (IRRs) despite premedication
with corticosteroids and antihistamine drugs. IRRs were mild
moderate and occurred during the second cycle. The most common
symptoms were fever, dyspnea, nausea and rash. One patient
experienced grade 2 neutropenia and received prophylactic growth
factor support.
Conclusions:
1. The combination of BV and bendamustine has shown benefit
as first salvage regimen for relapsed and refractory HL, improving the
overall response rate and CR rate prior to ASCT to 91% and 75%
respectively in our experience.
2. The treatment was well tolerated. Adverse events were mostly
IRRs of mildmoderate intensity. In order to control IRRs a desensi-
tization protocol was applied to all patients from the second cycle on.
No patient had to discontinue therapy due to adverse events.
TABLE 1Patient characteristics and results
Appendix
SUPPLEMENT ABSTRACTS
-
441
REFERENCES
1. LaCasce AS, et al. Brentuximab vedotin plus bendamustine: a
highly active first salvage regimen for relapsed or refractory
Hodgkin lymphoma. Blood. 2018 Jul 5;132(1):4048.
Keywords: Hodgkin lymphoma, Combination Therapies
No conflicts of interests pertinent to the abstract.
354 |BRENTUXIMAB VEDOTIN FOR TREATMENT IN PATIENTS
WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN
LYMPHOMA IN A REAL WORLD SETTING: CLINICAL OUTCOMES
AND IMPACT ON QUALITY OF LIFE
T. Ionova
1
, M. Andrievskikh
2
, A. Amdiev
3
, E. Baryakh
4
, V. Chang
5
, A.
Endakova
6
, N. Fadeeva
7
, G. Husainova
8
, V. Ivanov
9
, K. Kaplanov
10
, O.
Kaverina
11
, M. Kiseleva
3
, T. Klitochenko
12
, V. Kurakin
13
, O.
Larionova
14
, D. Lazareva
11
, K. Lepik
15
, I. Lysenko
16
, V.
Melnichenko
17
, N. Mikhailova
15
, R. Minullina
8
, O. Mironov
5
, E.
Misyurina
4
, N. Mochkin
17
, T. Nikitina
1
, Y. Osipov
18
, T. Petrova
8
, N.
Porfirieva
1
, O. Rukavitsyn
19
, R. Safin
8
, A. Samoylova
17
, T.
Shelekhova
20
, D. Sherstnev
20
, P. Simashova
19
, E. Smirnova
17
, N.
Trenina
13
, E. Vasiliev
21
, E. Volodicheva
22
1
Multinational Center for Quality of Life Research, Department of
Hematology, Saint Petersburg, Russian Federation,
2
Chelyabinsk Regional
Clinical Center of Oncology and Nuclear Medicine, Hematology,
Chelyabinsk, Russian Federation,
3
V.M. Efetov Crimean Republican
Oncology Center, Hematology, Simferopol, Russian Federation,
4
City
Clinical Hospital 52, Hematology, Moscow, Russian Federation,
5
Tambov Regional Oncological Clinical Center, Hematological, Tambov,
Russian Federation,
6
Kirov Research Institute of Hematology and Blood
Transfusion under the Federal Medical Biological Agency, Hematological,
Kirov, Russian Federation,
7
Chelyabinsk Regional Clinical Center of
Oncology and Nuclear Medicine, Hematology, Saint Petersburg, Russian
Federation,
8
Republican Clinical Oncology Center of the Ministry of
Health of the Republic of Tatarstan, Hematological, Kazan, Russian
Federation,
9
Almazov National Medical Research Centre, Department of
Anesthesiology and Intensive Care Medicine, Saint Petersburg, Russian
Federation,
10
S.P. Botkin City Clinical Hospital, Hematological
Department, Moscow, Russian Federation,
11
Altai Regional Oncology
Center, Hematological Department, Barnaul, Russian Federation,
12
Volgograd Regional Clinical Oncological Center, Hematological
Department, Volgograd, Russian Federation,
13
Clinical Oncological
Center, Hematological Department, Omsk, Russian Federation,
14
Primorskiy Regional Oncologic Center, Hematological Department,
Vladivostok, Russian Federation,
15
RM Gorbacheva Research Institute of
Pediatric Oncology, Hematology and Transplantation, Pavlov University,
Chemotherapy and Bone Marrow Transplantation Department, Saint
Petersburg, Russian Federation,
16
National Medical Research Centre for
Oncology of the Ministry of Health of Russia, Department of
Oncohematology, RostovonDon, Russian Federation,
17
N.I. Pirogov Na-
tional Medical Surgical Center, Department of Hematology and Chemo-
therapy with a room of Bone Marrow and Hematopoietic Stem Cells
Transplantation, Moscow, Russian Federation,
18
Almazov National Med-
ical Research Centre, Department of Oncohematology, Saint Petersburg,
Russian Federation,
19
N.N. Burdenko Main Military Clinical Hospital,
Hematological Center, Moscow, Russian Federation,
20
Clinic of Profes-
sional Pathology and Hematology named after V.Ya. Shustov, Saratov
State Medical University, Hematology, Saratov, Russian Federation,
21
Regional Clinical Hospital, Hematological Department, Krasnoyarsk,
Russian Federation,
22
Tula Regional Clinical Hospital, Hematological
Department, Tula, Russian Federation
One of the approved treatment options for pts with relapsed/re-
fractory classical Hodgkin Lymphoma (rrcHL) is brentuximab vedo-
tin (BV). Comprehensive evaluation of treatment effects of
brentuximab vedotin (BV) in pts with rrcHL, including clinical and
patientreported outcomes, is worthwhile. We aimed to evaluate
clinical outcomes and quality of life (QoL) in rrcHL pts receiving BV
in the real world setting.
Pts with rrcHL receiving BV 1.8 mg/kg q3w were included in the
multicenter realworld study. Treatment response was assessed us-
ing RECIST criteria v. 1.1. The KaplanMeier method was used to
estimate progression free survival (PFS). For assessment of adverse
events (AEs) NCI CTCAE v. 4.0 was used. For QoL assessment pts
filled out RAND SF36. Generalized Estimating Equations (GEE) and
McNemar's test were applied.
In the total 70 pts with rrcHL were enrolled in the study. The
analysis was carried out in two groups. Group 1 included 62 pts
who were ineligible for ASCT or relapsed after ASCT median age
31 yrs, 53% males; 50% had IV stage; 66% Bsymptoms; 18%
ECOG 23; 19% pts in Group 1 relapsed after ASCT. Group 2
consisted of 8 pts who received BV following ASCT median age
28 yrs, 63% males; 25% had IV stage; 13% Bsymptoms; no pts
with ECOG 23. All the pts received 2 previous treatment lines
(210). Before BV treatment start 60% pts in Group 1 and 38% pts
in Group 2 had severe/critical QoL impairment. In Group 1 at
median followup of 8 mo, 68% pts achieved/maintained objective
response (OR). Among them 40% pts achieved complete remission
(CR) and 28% partial remission (PR). The median PFS in Group 1
was 10.6 mo (95% CI: 7.412.9). In Group 2 at median followup of
15 mo 7/8 pts achieved/maintained OR; among them 6 pts had CR
and one PR. The median PFS in Group 2 was not reached. The
most common AEs were peripheral neuropathy and fatigue (55%
and 36%). AEs of grades IIIIV in Group 1 were reported in one
patient (1.6%), SAE one case (sepsis, respiratory insufficiency due
to agranulocytosis), in Group 2 in 2 pts; one case of SAE in Group
2 was registered (abdominal syndrome). In Group 1 during BV
treatment QoL improved by all SF36 scales (GEE, p <.01) with the
most pronounced increase of role physical functioning (∆=60) and
role emotional functioning (∆=44) as compared to baseline. Propor-
tion of pts with severe/critical QoL impairment significantly
decreased during BV treatment (p <.05). In Group 2 QoL stabili-
zation or improvement was obtained during BV treatment; number
of pts with severe/critical QoL impairment slightly diminished as
compared to baseline.
442
-
SUPPLEMENT ABSTRACTS
The results support the notable efficacy and good tolerability of
BV for treatment of rrHL in the reallife setting. Treatment with BV
has positive impact on QoL in rrcHL pts. Improvement of QoL is a
valuable outcome of BV treatment and supports patient
centeredness approach in treatment decisionmaking in this pa-
tient's population.
The research was funded by: IIR funded by Takeda
Keywords: Hodgkin lymphoma, Immunotherapy
Conflicts of interests pertinent to the abstract
T. Ionova
Other remuneration: Principle investigator of the IIR
355 |EVALUATION OF RESPONSE TO THE FIRSTLINE
THERAPY OF PATIENTS WITH CLASSICAL HODGKIN
LYMPHOMA BASED ON INTERIM PETCT AT A PRIVATE
BRAZILIAN INSTITUTION
J. M. De Almeida
1
, A. Alves
2
1
Instituto Hemomed de Oncologia e Hematologia, Clinical Department,
São Paulo, Brazil,
2
Instituto Hemomed de Oncologia e Hematologia,
Presidency, São Paulo, Brazil
Introduction: In Brazil the firstline therapy for Hodgkin lymphoma is
generally performed with ABVD protocol, being treatment strategies
guided by PETCT not commonly adopted. Epidemiological and
treatment data on the disease is scarce, coming mostly from public
health services.
Methods: Retrospective study of patients with classical Hodgkin
lymphoma, who were diagnosed and treated from 01/01/2016 to 12/
31/2020. Were included all patients registered on electronic health
records of the Hemomed Institute of Oncology and Hematology with
ICD.10 C81, above 18 years and with at least 3 years of follow up.
They were classified according to Clinical Stratification Criteria
considering Ann Arbor Staging and Laboratory Markers. Then ana-
lysed the rates of Complete Response at the end of the firstline
treatment with AVBD protocol +/radiotherapy, considering strati-
fication at diagnosis and response rates on the occasion of interim
PET.
Results: 46 patients were eligible, being 69.5% female. The mean age
of diagnosis was 32 years old. Regarding staging, 43.4% presented
stage I or II and 56.6% stage III or IV. 32.6% of patients presented
bulky mass, 13% in stages I or II. 65% presented Advanced Stage
Disease according to the criteria by the European Organization for
Research and Treatment of Cancer (EORTC). PETCT was performed
for initial staging in 80% and interim PET in 87% of patients. Among
patients with Early Stage Disease, 80% presented a complete
response (CR) in interim PET. Of the 28 patients of the Advanced
Stage Disease Group, 19 (68%) had a CR in interim PET and 9 (32%)
had a Partial Response (PR). Analysis of response to treatment
according to classification and interim PET shows that in the Early
Stage Groups all patients had CR in PET by the end of treatment,
including those who had obtained PR in interim PET previously.
However, in the Advanced Stage Group, of the 19 (68%) patients that
had CR in interim PET, only 16 (57%) maintained CR at the end of the
treatment. Out of the 9 (32%) patients with PR in interim PET, 5
(18%) did not have CR at the end of the treatment, taking into
consideration the fact that the data was not available for 1 of the
patients.
Conclusion: Patients from Early Stage Groups, being favorable or
unfavorable, obtained a high percentage of CR with the use of ABVD
+/radiotherapy. However, Advanced Group patients that continued
with ABVD, especially those with positive interim PET, presented a
high rate of refractory or early relapse. Such finding reinforces the
prognostic value of positive interim PET in Advanced Group patients
and the need to intensify therapy in these patients. This strategy is of
key importance to reducing the need for rescue therapy.
Keywords: PETCT, Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
J. M. De Almeida
Other remuneration: Aché Laboratórios Farmacêuticos S. A.
356 |THE ROLE OF END OF TREATMENT PET CT EVALUATED
BY DEAUVILLE FIVEPOINT SCALE AS PROGNOSTIC ROLE IN
HODGKIN LYMPHOMA
G. M. Assanto
1
, R. Agrippino
1
, G. Lapietra
1
, M. L. De Luca
1
, A.
Chiaravalloti
2
, G. Annechini
1
, G. M. D'Elia
1
, G. Ciotti
1
, M. Martelli
1
, A.
Pulsoni
1
1
Haematology, Department of Translational and Precision Medicine,
Sapienza University of Rome, Rome, Italy,
2
Nuclear medicine, Department
of Biomedicine and Prevention, Nuclear Medicine, University Tor Vergata,
Rome, Italy, Rome, Italy
Introduction: Positron Emission Tomography/Computed Tomogra-
phy (PET CT) is crucial in staging and response assessment in
Hodgkin lymphoma (HL). While early tumor response is assessed
through an interim PET (IPET) by Deauville 5point scale (DS), end of
treatment (EoT) PET CT is used to evaluate absence or presence of
metabolic disease, lacking scientific evidence of a correlation be-
tween specific DS and prognosis. Our study aimed to analyse EoT
PET CT response to demonstrate a possible prognostic correlation
between DS and patient prognosis in terms of Relapse Free Survival
(RFS) and Overall Survival (OS).
Methods: We conducted a monocentric retrospective study in pa-
tients with Classic HL, consecutively treated with ABVD between
2007 and 2018 with at least 1 year of followup and with favourable
IPET (DS13). EoT and IPET CT images were collected and sub-
mitted to blind central revision and DS assessment. Different values
of DS at EoT PET CT were compared in terms of PFS. Survival
SUPPLEMENT ABSTRACTS
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443
analysis was performed by KaplanMeier curves and LogRank test.
Statistical significance was considered for values of p <0.05.
Results: PET CT images of 78 patients were centrally reviewed. All
patients are currently alive (OS=100%). After a median followup of
60 months (range 17139) 17 patients (21%) had disease recurrence,
with RFS of 60% at 104 months (median not reached). The median
time to relapse was 8 months (range 339). Splenic involvement,
anemia (Hb<12 gr/dl) and bulky disease at diagnosis increased risk of
relapse. Patients with EoT DS1 (56 cases) showed 83% RFS at 100
months (median not reached). Median RFS worsened for higher DS:
77 months for DS2 (12 cases), 2 months for DS3 (2 cases), 26 months
for DS 4 (3 cases), and 14 months for DS5 (p <0.001) [Shown in
figure]. There was a longer time frame to relapse in DS1/2 compared
to DS3 (median time of 34 and 4 months respectively). Comparing I
PET DS with EoT PET DS, higher RFS was observed in stable or
reduced metabolic activity, unlike worsened DS indicates increased
risk of relapse (p <0.001).
Conclusion: Our study suggests that a systematic evaluation of EoT
PET according to DS allows more accurate identification of patients
with an unsatisfactory metabolic response and a better prognostic
stratification. The joint evaluation of the IPET and EoT PET data
shows a higher risk of recurrence in case of increased DS. In patients
ending treatment with a persistently significant FDG uptake some
form of consolidation could be investigated.
Figure Relapse free survival (RFS) according to End of Treatment
(EoT) score of Deauville 5point scale (DS): patients with a DS 1 show
a better prognosis. A DS progressively higher is indicative of residual
metabolic uptake and is associated with an increased risk of relapse
(p <0.001).
Keywords: Diagnostic and Prognostic Biomarkers, PETCT, Hodgkin
lymphoma
No conflicts of interests pertinent to the abstract.
357 |A PROSPECTIVE UKRAINIAN MULTICENTRE COHORT
STUDY OF PET VALUE PROGNOSTIC ROLE IN PRIMARY
PATIENTS WITH HODGKIN LYMPHOMA (HL): HIGHLIGHTING
CLINICAL RELEVANCE
O. Novosad
1
, I. Pastushenko
1
, O. Gorbach
1
, V. Kozlov
2
, L.
Mykhalska
3
, O. Kindrakevych
3
, M. Novikov
4
, O. Karnabeda
5
, O.
Oliinichenko
6
, Y. Kmetyuk
7
, O. Karpova
7
, A. Ashykhmin
8
, T. Rudiuk
9
,
I. Kriachok
1
1
National Cancer Institute, Oncohematology, Kyiv, Ukraine,
2
Regional
Clinical Hospital, Hematology, Odessa, Ukraine,
3
Clinical Hospital
“Feofaniya”, Center of Hematology, Kyiv, Ukraine,
4
Oncology Hospital
“LISOD”, Radiology, Kyiv, Ukraine,
5
Hospital of Oncology “Innovacia”,
Hematology, Kyiv, Ukraine,
6
Center of Nuclear Medicine, Radiology, Kyiv,
Ukraine,
7
Clinical Hospital “Feofaniya”, Radiology, Kyiv, Ukraine,
8
National Cancer Institute, Radiology, Kyiv, Ukraine,
9
Bogomolets
National Medical University, Oncology, Kyiv, Ukraine
Introduction: Using PET in a metabolic response assessment has
provided an opportunity of individualized treatment for patients with
newly diagnosed HL. Current risk assessment systems cannot pro-
vide a reliable prediction of failure in an individual treatment. The
primary endpoints were to assess a correlation between PET findings,
regimens, IPS and survival, as well as whether there is a difference
when patient treatment is intensified or not intensified depending on
PET findings.
Methods: This substudy was conducted in a scope of a broader
prospective multicenter study on the predictive value of PET
response assessment (205 patients with HL, up to 69 years of age).
444
-
SUPPLEMENT ABSTRACTS
Patients received a treatment with ABVD or BEACOPP14/esc or
“switchedregimens” (ABVD+BEACOPPesc/14, BEACOPPesc/14
+ABVD). PET imaging was performed using Deauville criteria pro-
tocol for response assessment. According to IPS, 155 (75.6%) pa-
tients had 2 and 50 (24.4%) patients had 34 risk factors (low and
high risk groups, respectively, p <0.05).
Results: The ORR was 91.7%. The ORR for patients with stage III
was 95.5% (106/111) vs 87.2% (82/94) for patients with stage IIIIV.
In total, the disease progression occurred in 48.3% (15/31) of
interim PETpositive (PET2+) patients and 11.5% (20/174) of interim
PETnegative (PET2) patients (p <0.05). We confirmed a significant
difference between the 5year event free survival (EFS) rate for
patients with PET2+vs PET2. Thus, PET2patients with early and
advanced stages had an EFS level much higher than the PET2+pa-
tient group (87% and 85% vs 55% and 15% respectively, Logrank
test, p =0.0001).
Using ABVD and “switchedregimens” for IIIstage patients did
not reveal a significant correlation to the 5year EFS. However, a more
intensified treatment for patients with stage IIIIV of HL showed a
significantly better level of EFS compared to the ABVD regimen, and it
did not depend on PET2 status (Logrank test, p =0.0003). Moreover,
intermediaterisk group cohort (2B stage) tends to improve the EFS
levels when the regimens was given BEACOPPesc/14+ABVD vs
ABVD+BEACOPPesc/14 vs ABVD (80% vs 60% vs 55% respectively,
p=0.064) and was independent of PET2 status.
Patients in low risk group were associated with significant
improvement in 5year EFS compared with patients in high risk group
(83% vs 50%, respectively, p =0.01). The estimated 5year EFS was
85% in PET2vs 45% with PET2+in low risk group (p <0.0001). The
same result was found in high risk group patients (82% vs 50%,
p<0.0001).
Conclusion: Our results of PET2 and PET3 remains very important in
the early detection of highrisk patients treated with standard
chemotherapy regimens, who are unlikely to show a complete
response to therapy, which may justify intensification of treatment at
that time, contributing to improved survival. According to IPS,
stratification still has an important role affecting the patients' with
HL survival.
EA previously submitted to regional or national meetings (up to
1000 attendees) and EHA 2021.
Keywords: PETCT, Hodgkin lymphoma, Chemotherapy
No conflicts of interests pertinent to the abstract.
358 |DO WE STICK TO INTERNATIONAL GUIDELINES WHEN
TREATING EARLY STAGE HODGKIN LYMPHOMA?
A. C. Oliver
1
, V. Irigoin
2
, V. Bradvica
3
, V. Lema
3
, A. I. Landoni
4
, C.
Ambrosoni
4
, P. Kollar
5
, A. Remedi
5
, S. Damiano
6
, P. Muxi
7
1
Hospital Británico, CASMU, Departamento de Hematología, Montevideo,
Uruguay,
2
COSEM, CASMU, Departamento de Hematología, Montevideo,
Uruguay,
3
Hospital Militar, Departamento de Hematología, Montevideo,
Uruguay,
4
Hospital Maciel, Departamento de Hematología, Montevideo,
Uruguay,
5
Medica Uruguaya, Departamento de Hematología, Montevideo,
Uruguay,
6
Instituto Nacional del Cancer, Departamento de Hematología,
Montevideo, Uruguay,
7
Hospital Británico, Departamento de
Hematología, Montevideo, Uruguay
Introduction: Early stage Hodgkin Lymphoma (HL) presents in >60%
of newly diagnosed patients, and cure is achieved in >90%. Since
2003 combined modality with chemo (CT) and radiotherapy (RT) has
been the standard of care and reduction of long term toxicities is a
priority. Several trials have proved the efficacy of reducing CT cycles
and dose of RT. The German HD10 trial showed that 2 ABVD plus
ISRT 20 Gy in favorable early stage HL was as effective as more
intensive treatment and is a widely recommended strategy. In 2015
RAPID trial showed that 3 ABVD when PET negative could be suf-
ficient. In stage III unfavorable HL, 4 ABVD plus ISRT or 6 ABVD are
classical options. The aim of our study is to analyze to what extent we
have adopted the management proposed by the guidelines in daily
practice in our country.
Materials: HL patients between 20112020 from the Uruguayan HL
Registry. 153 patients included, 68 stage III. Prognostic: German
Study Group factors.
Results: 68 patients: 27 male. Median age: 35.5 years (1583).
Nodular sclerosis: 52 (76.5%). Stage I: 11 (16.2%), stage II 57 (83.8%).
Favorable 37 (54.4%), unfavorable 31 (45.6%).
Stages III FAVORABLE: 36 patients. Male 14 (48.9%). Median
age 41 (1583). Stage I: 8 (22.2%), stage II: 28 (77.8%). 33 received
ABVD (91.7%), 2 AVD (5.6%), 1 supportive care.
Median number of cycles: 4 (26); stage I: 2(26), stage II: 4 (26).
2 ABVD +RT: 5 patients, 14.3 %
3 ABVD: 3; 2 +RT, 8.6%
4 ABVD: 12, 34.3 %; 4 +RT, 11.43%
6 ABVD: 13; 1 +RT, 37.2 %
2 AVD +RT: 1, 2.8 %
4 AVD: 1, 2.8 %
End of treatmentPET (EOTPET): 29 (80.6%). Complete
response (CR): 33 (91.7%). Median followup 40 months (0.7134), 1
relapse (2.8%), 2 deaths: 1 due to relapse, 1 due to untreated pro-
gression. 1 year Progression free survival (PFS) 97 %, 2 year Overall
Survival (OS) 92.9%.
Stages III UNFAVORABLE: 32 patients. Male 13 (30.6%). Me-
dian age: 30 (1575). Stage I: 3 (9.4%), II: 29 (90.6%). 31 received
ABVD (96.9%), 1 AVD (3.1%), 1 still on treatment. Median number of
cycles: 6 (18); stage I: 6 (46), stage II: 6 (18).
1 ABVD: 2 patients, 6,4 %
4 ABVD: 11, 35.5 %; 3 plus RT, 9.7 %
6 ABVD: 16; 4 plus RT, 51.7 %
8 ABVD: 1, 3.2 %
6 AVD: 1, 3.2 %
EOTPET: 22 (68.8%). CR: 21 (65.6%). Median followup 57.4
months (0.7142). 3 year PFS was 87%. 5 year OS 90.6%.
SUPPLEMENT ABSTRACTS
-
445
Conclusions: From 2011 and according to the HD10 study, RAPID
trial and NCCN guidelines stage III favorable HL should be treated
with ABVD x 2 +ISRT 20 Gy, 3 ABVD or 4 ABVD +ISRT. Only 34.3
% of our cohort of patients were treated according to any of these
recommendations. Regarding stage III unfavorable HL, guidelines
suggest ABVD x 4 +ISRT or 6 ABVD +/ISRT; 61.4% of our patients
were treated according to them.
This reflects that changes in traditional management of patients
take time to become standard in daily practice after evidence is
presented. Even though PFS and OS are comparable to international
data, we should improve our approach in order to reduce toxicity
without compromising results.
Keywords: Hodgkin lymphoma
No conflicts of interests pertinent to the abstract.
359 |ANALYSIS OF SPERMATOGENESIS BEFORE AND AFTER
TREATMENT IN PATIENTS WITH HODGKIN LYMPHOMA
F. Gaudio
1
, P. Masciopinto
1
, C. Nardelli
2
, M. P. Vacca
2
, F. E. Laddaga
3
,
E. Cicinelli
2
, P. Musto
1
1
AOUC Policlinico, Unit of Hematology and Stem Cell Transplantation,
Bari, Italy,
2
AOUC Policlinico, Unit of Second Unit of Obstetrics and
Gynecology, Bari, Italy,
3
AOUC Policlinico, Clinical Pathology Unit, Bari,
Italy
The outcome of patients with Hodgkin's lymphoma (HL) has
improved significantly in recent years, which is why attention has
increasingly been focused on the wellbeing of these young patients.
Consistent with this, the study aimed to analyze the influence of HL
and its treatment on spermatogenic status of young males and detect
new predictors influencing probability of parenthood.
In this retrospective study, spermatogenesis of 42 male patients
with HL (median age 25 years) treated at University Hospital of Bari
(Italy) between 2008 and 2016 was studied. Spermiogram was avail-
able in all patients at diagnosis, while in 24 spermiogram was also
available after therapy. All patients underwent ABVD as firstline
chemotherapy, of which 6 patients with relapsed/refractory disease
underwent autologous haematopoietic stem cell transplantation
(ASCT).
Results: At diagnosis, we found that 15 (35%) patients had normo-
zoospermia, 19 (45%) oligozoospermia, and 8 (19%) only other dys-
permic conditions.
Analyzing prognostic factors, we found that number of sperma-
tozoa at diagnosis was reduced in stage 34 (1.91x10e7 vs.
4.97x10e7; p =0.001); motility and vitality were reduced in stage 34
(motility: 29% vs. 43%, p =0.015; vitality: 49% vs 71%, p =0.011)
and in presence of B symptoms (motility: 30% vs. 44%, p =0.016;
viability: 53% vs. 69%, p =0.05); abnormal forms were increased in
patients with high ESR (84% vs. 75%, p =0.017) and albumin <4 (87%
vs. 75%, p =0.002).
After treatment, 17% of patients had azoospermia. Of the 9
normozoospermic patients at diagnosis, 5 (55%) maintained this
condition after treatment, while 4 (45%) developed azoospermia
associated with other types of dyspermia (all undergoing ASCT). Of
11 patients with oligozoospermia at diagnosis treated with first line
alone, 6 (54%) experienced normospermia after treatment. Further-
more, in patients who received only firstline treatment, the mean
sperm concentration increased after treatment (5.53x10e7 at diag-
nosis vs. 4.02x10e7 after treatment).
We also found that 4/6 patients undergoing ASCT had azoo-
spermia in the posttreatment control. On the other hand, 2 of
the 3 patients, who had oligozoospermia before treatment,
became normozoospermic after therapy. Furthermore, we found
that patients undergoing ASCT were associated with severe
impairment of fertility in terms of sperm motility (74% at diagnosis
vs. 22% after ASCT; p =0.025). In patients who did not undergo
ASCT we found a statistically significant improvement in fertility in
terms of motility (35% at diagnosis vs. 50% after treatment;
p=0.009)
Conclusions: In this study, we found that ASCT induced infertility in
the majority of male patients with HL and that first line treatment
could improve the fertility status caused by the disease. Further
studies are needed in a larger case series to investigate risk factors
for impaired fertility at diagnosis and after treatment
Keywords: Late Effects in Lymphoma Survivors
No conflicts of interests pertinent to the abstract.
PERIPHERAL T/NK CELL LYMPHOMAS
360 |BRENTUXIMAB VEDOTIN PLUS CHP AS FIRSTLINE
TREATMENT IN CD30 +PERIPHERAL TCELL LYMPHOMAS: REAL
LIFE EXPERIENCE FROM A SINGLE INSTITUTION IN SPAIN
E. Domingo Domenech
1
, J. M. Sancho Cia
2
, E. Gonzalez Barca
1
,
N. Kelleher
3
, M. RodriguezLuaces
4
, J. Rovira
5
, S. Verdesoto
6
,
M. Encuentra
1
, D. Blazevic
1
, A. Oliveira
1
, L. Escoda
5
, J. M. Ribera
2
,
A. Sureda
1
1
Institut Català d'Oncologia, Hospital Duran i Reynals, Institut
d'Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de Barcelona,
Hematology, L'Hospitalet de Llobregat, Barcelona, Spain,
2
Institut Català
d'Oncologia, Hospital Germans Trias i Pujol, Institut de Recerca contra
la Leucèmia Josep Carreras, Universitat Autònoma de Barcelona,
Badalona, Barcelona,Spain., Hematology, Badalona, Spain,
3
Institut
Català d'Oncologia, Institut d'Investigació Biomèdica de Girona
(IDIBGI), Universitat de Girona, Hematology, Girona, Spain,
4
Institut
Català d'Oncologia, Hospital de Tortosa Verge de la Cinta, Hematology,
Tortosa, Spain,
5
Institut Català d'Oncologia, Hospital Universitari
Joan XXIII, Hematology, Tarragona, Spain,
6
Institut Català
d'Oncologia, Hospital Moises Broggi, Hematology, Sant Joan d'Espí,
Barcelona., Spain
446
-
SUPPLEMENT ABSTRACTS
Introduction: Peripheral Tcell lymphomas (PTCL) are a heteroge-
neous group of lymphomas classically treated with CHOP or CHOP
like regimens, with poor outcomes. CD30 is universally expressed
and is pathognomonic in systemic anaplastic large cell lymphoma
(sALCL), with variable expression among nonsALCL PTCL subtypes
(4060%). Recent data of frontline treatment with Brentuximab
Vedotin (BV), an antiCD30 monoclonal antibody, plus CHOP has
demonstrated significant improvement in survival (ECHELON2
clinical trial), becoming the new standard of care for sALCL in Europe.
Patient and methods: From February 2019 to December 2020, 20
patients with de novo newly diagnosed CD30+PTCL have been
treated with the combination of BVCHP with primary prophylaxis
with GCSF, in the centers of the Catalan Institute of Oncology in
Spain. Survival curves were plotted by the KaplanMeier method.
Results: Clinical characteristics at diagnosis are shown in the table.
Of interest, 5 of the 10 ALK negative ALCL patients were diagnosed
of breast implant associated ALCL (BIAALCL) with extracapsular
involvement. The number of cycles administrated was 102, with a
median of 6 cycles per patient (range 16). At the time of this report,
2 patients were still on treatment. Seven cycles (7%) were delayed (3
due to infection, 2 due to neutropenia grade 2, and 2 due to causes
not related with chemotherapy). An adverse event was reported in
45 (44%) cycles, being the most frequent peripheral neuropathy in
14, nausea/vomiting in 9 and anemia in 8; all of them grade 12.
Treatment was discontinued after 1 cycle in 1 patient due to pro-
gression. Of the 18 evaluable patients, the overall response rate
(ORR) was of 83%, with 72% complete responses and 11% partial
responses. Consolidative autologous stem cell transplant (ASCT) was
performed in 5 patients. With a median followup of 14 months
(limits: 124), 1year progressionfree survival (PFS) and overall
survival (OS) was 68.2% (95% CI 44.691.7) and 82.2% (95% CI 63.9
100), respectively.
Conclusions: Brentuximab Vedotin plus CHP is an effective regimen
for CD30 positive PTCL, with a high rate of response. This combi-
nation presents a manageable safety profile, with the majority of
patients completing the planned treatment. The incidence and
severity of side effects are low, being peripheral neuropathy and
neutropenia the most frequent.
Keywords: Aggressive Tcell nonHodgkin lymphoma, Combination
Therapies
No conflicts of interests pertinent to the abstract.
361 |RISK MODEL FOR CENTRAL NERVOUS SYSTEM DISEASE
IN TLYMPHOBLASTIC LYMPHOMA: A SINGLECENTER
EXPERIENCE
X. Feng
1
, Y. Gao
1
, L. Li
1
, X. Li
1
, Z. Sun
1
, J. Wu
1
, X. Wang
1
, X. Fu
1
, L.
Zhang
1
, M. Zhang
1
1
The First Affiliated Hospital of Zhengzhou University, Department of
Oncology, Zhengzhou, China
Introduction: Tlymphoblastic Lymphoma (TLBL) represents for 2
4% of adult lymphoma, characterized by mediastinal mass and
young male predominance. Central nervous system (CNS) prophy-
laxis has become an integral part of all current acute lymphoblastic
leukemia treatment protocols. However, there is no consensus on
CNS prophylaxis in TLBL. Therefore, we retrospectively summa-
rized prognosis of CNS disease and risk factors for CNS relapse in
TLBL.
TABLE 1Clinical characteristics at diagnosis
SUPPLEMENT ABSTRACTS
-
447
Methods: We retrospectively collected 81 newly diagnosed TLBL
patients in our single institution from January 2015 to December
2019. CNS disease was diagnosed via contrasted magnetic resonance
imaging at the presence of typical symptoms, and/or detection of
lymphoma cells in the cerebrospinal fluid by either morphology or
immunophenotypes.
Fisher's exact test or chisquare test was used for discrete var-
iables, and t test or MannWhitney test was used for continuous
variables. KaplanMeier method was used to predict risk factors for
CNS disease. Statistical analyses were performed using SPSS, and p <
0.05 was considered to be statistically significant.
Results: Median age of the cohort was 25 years. 69 patients (85.2%)
were Ann Arbor IIIIV stage, 18 patients (22.2%) presented with B
symptom. 11 cases (22.4%) were identified as Early Tcell precursor
(ETP) LBL.
During a median followup of 20.5 months (3.060.5 months),
there were totally 10 patients (12.3%) diagnosed CNS disease. 3
cases (3.7%) were diagnosed at the initiation of treatment, 7 pa-
tients experienced CNS relapse during the treatment course. Me-
dian time to CNS disease was 7 months (020.0 months), and
median survival after CNS disease was 1.5 months (0.516.0
months).
The 2year progressionfree survival (PFS) of the entire cohort
was 39.63%, 2year overall survival (OS) was 54.11%. Median PFS
and OS of patients with CNS disease was much less than those
without CNS disease.
The univariable analysis showed elevated LDH, Ki6780%, ETP
phenotype and more than 2 sites of extranodal involvement pre-
dicted CNS disease. While the multivariable cox analysis revealed
that Ki6780% (HR =165.3, P=0.011), ETP phenotype (HR =31.1,
P=0.024) and more than 2 sites of extranodal involvement
(HR =21.4, P=0.037) were independent risk factors for CNS disease
in TLBL.
Subsequently, these three independent risk factors were com-
bined (1 point for each risk factor) to create a riskstratification
model called CNSLBL. Two CNSLBL subgroups were identified as
having low (01 risk factor), and high (23 risk factors). 38 cases
(69.1%) were lowrisk subgroup, 19 patients (30.9%) belonged to
highrisk group. 2year CNS relapse rates were 5.4% and 88.7%,
respectively (P=0.000), resulting in a 16.5 folds higher risk for CNS
relapse in the highvs lowrisk groups.
Conclusions: CNS disease displays a dismal prognosis in TLBL, and
our retrospective study generated a risk model to identify highrisk
populations.
The research was funded by: The study was supported by the
National Natural Science Foundation of China (Grant No.82000203)
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive Tcell
nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
362 |DERIVATION AND VALIDATION OF A NOVEL LIPID
COVERED PROGNOSTIC SCORING SYSTEM FOR NEWLY
DIAGNOSED MATURE T AND NK CELL LYMPHOMAS
T. Lu
1
, X. Fang
1
, Y. Jiang
1
, J. Liu
1
, Y. Cai
1
, S. Hu
1
, M. Ding
1
, X. Wang
1
,
X. Zhou
1
1
Shandong Provincial Hospital Affiliated to Shandong University,
Department of Hematology, Jinan, China
Introduction: Abnormal lipid metabolism was reported to influ-
ence the initiation and progression of malignancies. Nevertheless,
the significance of dyslipidemia in mature T and natural killer
(NK) cell lymphomas remains unexplored. This study aimed to
investigate the association between serum lipid metabolism level
and clinical outcomes, and further develop a lipidcovered prog-
nostic model for newlydiagnosed mature T and NK cell lym-
phoma patients.
Methods: A total of 173 patients (1/20066/2020) were enrolled in
the study, of which 115 constituted the training cohort while 58
composed the validation cohort. Univariate and multivariate Cox
regression analysis were performed to detect independent predictors
and generate a novel prognostic model, whose performance was
evaluated in the training and validation cohort from multiple aspects,
including Harrell's Cindex, calibration curves, KaplanMeier survival
analysis, timedependent receiver operating characteristic curves,
Brier score and decision curve analysis.
Results: Univariate analysis verified declined cholesterol (TC), high
density lipoprotein cholesterol (HDLC) and increased triglycerides
(TG) were associated with inferior survival outcomes in mature T and
NK lymphomas. Multivariate analysis revealed extranodal involved
sites2 (HR: 2.505; P=0.031), β2MG3mg/L (HR: 3.964; P=0.005)
and TC<3.58mmol/L (HR: 3.320; P=0.000) were three independent
predictors. Thus, a novel prognostic model, EnBC score, was estab-
lished with these three variables. EnBC score possessed satisfactory
discrimination and calibration since the Harrell's Cindex for OS
prediction was 0.840 (95% CI, 0.8100.870) and the calibration
curves showed an optimal agreement between the prediction and
actual observation. The prognostic significance of the novel model
was verified in KaplanMeier survival analysis by dividing patients
into four risk groups with different longterm survival (median OS, NA
vs. NA vs. 14.0 vs. 4.0 months, P<0.0001; median PFS, 84.0 vs. 19.0
vs. 8.0 vs. 1.5 months, P<0.0001) (Figure 1). Compared with the
present International Prognostic Index (IPI), EnBC score presented
better discrimination (timedependent AUCs of OS, EnBC 0.883
0.963 vs. IPI 0.7850.873, P<0.001) and better calibration (Brier
score of OS, EnBC 0.1460.271 vs. IPI 0.1540.296, P=0.023).
Moreover, the decision curve analysis showed that EnBC score pro-
vided larger net benefits than IPI in the entire patient population.
Conclusions: Serum lipid metabolism level was firstly demonstrated
significantly prognosisrelated in mature T and NK cell lymphomas.
448
-
SUPPLEMENT ABSTRACTS
Furthermore, a novel lipidcovered prognostic scoring system was
established and performed well in predicting the prognoses of
treatmentnaïve mature T and NK cell lymphoma patients.
Keywords: Diagnostic and Prognostic Biomarkers, Aggressive Tcell
nonHodgkin lymphoma
No conflicts of interests pertinent to the abstract.
363 |EXTRANODAL NK/TCELL LYMPHOMA, NASAL TYPE
AND HIV INFECTION: A MEXICAN DESCRIPTIVE SERIES
R. Castillollanos
1
, A. F. RamírezIbarguen
1
, C. LomeMaldonado
2
1
Instituto Nacional de Cancerología, Hematología, Mexico City, Mexico,
2
Instituto Nacional de Cancerología, Hematopathology, Mexico City,
Mexico
SUPPLEMENT ABSTRACTS
-
449
Introduction: Extranodal NK/Tcell lymphoma, nasal type (ENKL), is
a rare and aggressive lymphoma, characterized by an extranodal
involvement with midfacial destruction, primarily in nasal and
paranasal structures, and is highly associated with EpsteinBarr
virus (EBV). It is an uncommon lymphoma with higher incidence
in Asian and South American countries. Infection with Human
Immunodeficiency Virus (HIV) is a known risk factor for develop-
ment of nonHodgkin lymphoma. In most of the cases are Bcell
types, with a smaller percentage being Tcell lymphomas. There
are few case reports of this association, and no large series was
found.
Methods: It was made a research on a data base of all lymphomas
and HIV from 2010 to 2020, ENKL pathology diagnose and HIV
diagnosed confirmed by a 4th gen ELISA cases were selected. Clinical
data from the electronic medical records were extracted. The main
objective was to describe the clinical characteristics of our HIV and
ENKL series.
Results: Of a total of 258 cases of lymphoma plus HIV, 7 (2.7%)
belonged to newly diagnostic of ENKL. The median age at lymphoma
diagnosis was 39 years (21 57) and all were male. Four of the patients
knew his HIV status at diagnosis, the other three were diagnosticated
at the same time of the lymphoma diagnosis. Only three of the patients
known as a HIV positive were on High Activity Antiretroviral Therapy
(HAART) at the diagnosis, the rest start HAART after diagnosis. At the
diagnosis of ENKL only 2 patients had a CD4 count >150 cells, and
only 2 had undetectable viral load; in one patient this was not deter-
mined at diagnosis. In all patients the ENKL was nasal type, only one
patient presented with a stage IV for lung involvement, 2 patients were
stage II by nodal involvement, the rest were localized at midfacial
structures. All cases were associated with EBV with EBER positive, 3
cases were positive for CD30. Regards to treatment, one patient died
before treatment because AIDS complications and six patients
received treatment with Lasparaginase based chemotherapy (CHT)
(SMILE, LVP, GeLOx, Asp/Met/Dex). Three of patients received CHT
followed by radiotherapy (RT) with a median dose of 44 Gy (36 55),
these patients achieve complete response. One more present pro-
gression at central nervous system (SNC) after two cycles of Asp/Met/
Dexa protocol and went to second line but died for infective compli-
cations 11 months after diagnosis. Two patients received one or two
cycles and lost follow up before ended treatment. At the end, 3 pa-
tients still alive with mean follow up was 16 months (2 61).
Conclusions: ENKL is highly associated with EBV and actually we
know that HIV patients may have early exposition to EBV. A few has
been written about ENKL and HIV association, for this we describe
the clinicopathologic characteristics of our patients with these
concomitant diseases. It's important to note the rate of CD30 pre-
sent in our patients for the role of therapeutic target.
Keywords: Aggressive Tcell nonHodgkin lymphoma, Extranodal
nonHodgkin lymphoma, NonHodgkin (Pediatric, Adolescent, and
Young Adult)
No conflicts of interests pertinent to the abstract.
NEW DRUGS
364 |THE CD19/CD3 BISPECIFIC ANTIBODY WORK
EFFECTIVELY AS ADJUNCT WITH IBRUTINIB ON THE
TREATMENT OF BCELL LYMPHOMA
H. Yu
1
, W. Liu
1
, L. Mi
1
, S. Shu
1
, W. Zhang
2
, Z. Ying
1
, H. Chen
3
, X. Yan
3
,
W. Shen
3
, G. Tu
3
, Y. Ye
1
, M. Li
1
, D. Wang
1
, D. Hu
1
, J. Cao
1
, F. Qi
1
,
X. Wang
1
, Y. Song
1
, J. Zhu
1
1
Beijing Cancer Hospital, Lymphoma, Beijing, China,
2
Beijing Cancer
Hospital, Molecular Oncology Laboratory, Beijing, China,
3
ITabMed Ltd,
Preclinical Research, Shanghai, China
Introduction: Targeting CD19, a significant surface marker of B cell
malignant cells, with antiCD19/CD3 bispecific antibodies became
new choices in B cell hematological malignancies. Blinatumomab as the
first generation CD19/CD3 bispecific antibody (bsAb) was approved
for the treatment of relapsed or refractory Bcell precursor acute
lymphoblastic leukemia. However, it also has its own limitations,
including side effects and limited efficacy. Bruton tyrosine kinase
(BTK) inhibitor, ibrutinib has been shown to inhibit the IL2induced
tyrosine kinase (ITK) which expressed in T and NK cells. This inhibi-
tion could result in modulation of cytokine production by T cells. Here
we reported a newly designed CD19/CD3 bispecific antibody (A319)
with similar mechanism of action as blinatumomab. To further improve
the efficacy and reduce side effects, we tried to combine ibrutinib with
A319, and explore the biological effects and the mechanisms of
enhanced efficacy and reduced CRS in vitro and in vivo.
Methods: A319 was provided by ITabMed Ltd (Shanghai, China).
CFSE was used to evaluate the proliferation of T cells, and CD25/CD69
staining was applied to assess the activation of T cells induced by A
319. Supernatant from cocultured tumor and T cells was collected
and measured for lactate dehydrogenase (LDH) lysis to measure
cytotoxicity. Humanized mice model were built by human PBMC in-
jection into NOG mice. To build CRS model, we allowed Raji derived
tumor to grow up to 600800mm3, at which point we dosed mice with
high dose A319(20μg/kg). Tube formation assay using HUVEC cells
was performed to explore the effects of ibrutinib on angiogenesis.
Results: A319 effectively induced CD19positive tumor cell lysis.
The regression analysis presented a significant correlation between
CD19 expression of target cells and the sensitivity to A319
(p <0.01). Exposure T cells to A319 enhanced T cell proliferation
and promoted T cell activation (CD25+CD69+T cells) significantly.
Moreover, A319 produced remarkable antitumor effects in vivo
though companied by CRS. Interestingly, the addition of ibrutinib
inhibited A319 induced CRS and improve the antitumor efficacy in
vitro and in vivo. Experiments exploring the mechanisms of the
combined effects showed that ibrutinib could inhibit the infiltration
of M2 (CD163, Arg1) macrophage and normalize vascular (CD34+α‐
SMA+) in vivo compared with A319. The in vitro results also pre-
sented that ibrutinib could polarize macrophage into M1 (CD80,
CD86, iNOS). Tube formation assay on HUVEC cells proved that
ibrutinib could inhibit macrophage mediated tube formation.
450
-
SUPPLEMENT ABSTRACTS
Conclusions: We found that A319 could greatly activate T cells and
promote the proliferation of T cells from patients. The addition of
ibrutinib effectively enhanced the antitumor effects and lower the
CRS of A319 possibly through the regulation of macrophage medi-
ated angiogenesis.
Keywords: Tumor Biology and Heterogeneity, Combination Thera-
pies, Immunotherapy
No conflicts of interests pertinent to the abstract.
365 |PRECLINICAL EVALUATION OF EPCORITAMAB
COMBINED WITH STANDARD OF CARE AGENTS FOR THE
TREATMENT OF BCELL LYMPHOMAS
C. W. Chiu
1
, I. H. Hiemstra
2
, W. ten Hagen
2
, R. SnijdewintNkairi
2
, B.
de Jong
2
, P. Garrido Castro
2
, C. Kweekel
2
, R. S. Oliveri
3
, B. Elliot
4
, M.
WielgosBonvallet
1
, E. SzaferGlusman
5
, D. Schuurhuis
2
, J. Blaedel
3
,
T. Ahmadi
4
, E. Breij
2
, A.K. Sasser
1
, M. JureKunkel
1
1
Genmab US, Inc., Translational Research, Plainsboro, New Jersey, USA,
2
Genmab B.V., Translational Research, Utrecht, Netherlands,
3
Genmab A/
S, Oncology, Copenhagen, Denmark,
4
Genmab US, Inc., Oncology,
Plainsboro, USA,
5
Abbvie, Translational Oncology, Sunnyvale, California,
USA
Introduction: Bcell nonHodgkin lymphoma (BNHL) has a high
unmet medical need for efficacious, well tolerated, offtheshelf
therapies that can combine with standard of care (SOC) regimens.
Epcoritamab (DuoBody
®
CD3CD20) is a subcutaneously (SC)
administered bispecific antibody with a manageable safety profile
and promising preliminary antitumor activity in aggressive and
indolent BNHL. Epcoritamab simultaneously binds to CD3 on T
cells and CD20 on tumor cells to induce potent Tcellmediated
killing. SOC treatments for BNHL include GEMOX (gemcitabine
and oxaliplatin), or rituximab in combination with chemotherapy
regimens such as CHOP (cyclophosphamide [CPA], doxorubicin
[DOX], vincristine [VINC] and prednisone [PRD]), bendamustine, or
immunomodulatory agents such as lenalidomide (LEN). These ther-
apies have mechanisms of action distinct from epcoritamab and
mostly nonoverlapping adverse event profiles. Preclinical studies
showed that epcoritamab's antitumor activity is retained in the
presence of a rituximab analog. Here, we present in vitro data of
epcoritamab in combination with components of current SOC
therapies for BNHL.
SUPPLEMENT ABSTRACTS
-
451
Methods: Healthy donor T cells (effector cells) and/or CD20
expressing BNHL tumor cell lines were pretreated with SOC com-
ponents (LEN, CPA, DOX, VINC or PRD) to evaluate the impact on T
cells and target cells. Pretreated T and BNHL cells were incubated
with the same SOC in the presence of epcoritamab, and Tcell
mediated cytotoxicity and associated Tcell activation were
assessed by flow cytometry. Bendamustine or GEMOX was added
with epcoritamab during the Tcell activation and cytotoxicity assay
to assess potential antagonizing effects.
Results: LEN enhanced Tcell activation induced by CD3 crosslinking
with immobilized antiCD3 or epcoritamab, resulting in higher potency
of these T cells to exert epcoritamabinduced cytotoxicity of CD20
expressing tumor cells. T cells pretreated with individual CHOP
components could mediate epcoritamabinduced cytotoxicity. Finally,
bendamustine and GEMOX did not antagonize Tcell activation and
increased Tcellmediated cytotoxicity induced by epcoritamab.
Conclusion: These preclinical data support further exploration of
combination of epcoritamab with these SOC agents in clinical trials.
Given the promising singleagent activity of SC epcoritamab, and
distinct safety profile, these combinations may lead to further
deepening of treatment responses and transform longterm outlook
for BNHL patients. Epcoritamab in combination with these SOC
agents is currently being evaluated in a clinical trial (NCT04663347).
EA previously submitted to AACR 2021.
The research was funded by: Genmab US, Inc.
Keywords: Combination Therapies
Conflicts of interests pertinent to the abstract
C. W Chiu
Employment or leadership position: Genmab US, Inc.
Stock ownership: Genmab US, Inc.
I. H Hiemstra
Employment or leadership position: Genmab
Stock ownership: Genmab
W. ten Hagen
Employment or leadership position: Genmab
R. SnijdewintNkairi
Employment or leadership position: Genmab
B. de Jong
Employment or leadership position: Genmab
P. Garrido Castro
Employment or leadership position: Genmab
C. Kweekel
Employment or leadership position: Genmab
R. S Oliveri
Employment or leadership position: Genmab
Stock ownership: Genmab
B. Elliot
Employment or leadership position: Genmab
Stock ownership: Genmab
M. WielgosBonvallet
Employment or leadership position: Genmab
E. SzaferGlusman
Employment or leadership position: Abbvie
D. Schuurhuis
Employment or leadership position: Genmab
J. Blaedel
Employment or leadership position: Genmab
Stock ownership: Genmab
T. Ahmadi
Employment or leadership position: Genmab
Stock ownership: Genmab
E. Breij
Employment or leadership position: Genmab
Stock ownership: Genmab
A K. Sasser
Employment or leadership position: Genmab
Stock ownership: Genmab
M. JureKunkel
Employment or leadership position: Genmab
Stock ownership: Genmab
366 |IRONOMYCIN KILLS DIFFUSE LARGE BCELL
LYMPHOMA CELLS BY TARGETING CELLULAR IRON
HOMEOSTASIS
J. Devin
1
, T. Cañeque
2
, Y.L. Lin
1
, L. Mondoulet
3
, J.L. Veyrune
4
, M.
Abouladzé
1
, E. Garcia de Paco
1
, O. Gadacha
1
, G. Cartron
5
, P. Pasero
1
,
C. Bret
6
, R. Rodriguez
2
, J. Moreaux
1
1
IGHCNRSUMR 9002, Institute of Human Genetics, Montpellier, France,
2
CNRS UMR 3666. INSERM U1143, Chemical Biology of Cancer Labo-
ratory, Paris, France,
3
Sideros, Paris, France,
4
CHU Montpellier, UTC,
Montpellier, France,
5
CHU Montpellier, Clinical Hematology, Montpellier,
France,
6
CHU Montpellier, Biological Hematology, Montpellier, France
Introduction: Diffuse large B cell lymphoma (DLBCL) is the
most common hematological malignancy. Although more than half of
these patients may achieve longterm remission, the majority of
the remaining patients succumb to DLBCL. Abnormal iron homeostasis
452
-
SUPPLEMENT ABSTRACTS
is implicated in carcinogenesis and in the progression of many tumors.
Thus, we searched for a putative altered iron homeostasis in DLBCL
that could be exploited to develop novel therapeutic strategies.
Method: In this study, we analyzed the iron metabolism gene expres-
sion profile (GEP) of large cohorts of DLBCL patients. We also analyzed
the effect and mechanism of action of ironomycin, a synthetic deriva-
tive of salinomycin that presents an antineoplastic effect on breast
cancer stem cells by accumulating and sequestering iron in lysosomes.
We used a large panel of 16 DLBCL cell lines and primary samples from
patients collected after patients' written informed consent in accor-
dance with the Declaration of Helsinki and institutional research board
approval.
In vivo validation was investigated using the A20 syngeneic
immunocompetent model of murine lymphoma. We also investigated
the effect of ironomycin combined with conventional drugs
commonly used in DLBCL. Ironomycinassociated hematopoietic
toxicity was investigated in vitro using hematopoietic progenitor
colonyforming unit assays.
Results: We established the Iron Score (IS), a gene expressionbased
risk score (validated in 4 independent cohorts of patients) allowing to
identify DLBCL patients with a poor outcome and that could benefit
from a suitable targeted therapy. We analyzed the therapeutic
benefit of ironomycin, a new promising lysosomal iron targeting small
molecule. Ironomycin inhibited DLBCL cell proliferation in a panel of
16 DLBCL cell lines, at nanomolar concentrations compared to
typical iron chelators. Ironomycin induced significant cell growth in-
hibition, ferroptosis and autophagy in DLBCL cells. Upon ironomycin
treatment, we also identified DNA double strand break accumulation,
delayed progression of replication forks and a significant increase of
RPA2 phosphorylation that is a marker of replication stress. Impor-
tantly, ironomycin significantly reduced the median number of viable
primary DLBCL cells of patients without major toxicity for nontumor
cells from the microenvironment and presented a low toxicity on
hematopoietic progenitors compared to conventional treatments.
Interestingly, we identified a significant synergistic effect by
combining ironomycin with Doxorubicin, BCL2, BTK or Syk inhibitors.
Conclusion: Altogether, these data demonstrate that a subgroup of
highrisk DLBCL patients can be identified with the IS, which can
potentially benefit from targeting iron homeostasis.
The research was funded by: The R.R. research group is funded by
the European Research Council (ERC) under the European Union's
Horizon 2020 research and innovation programme (grant agreement
No [647973]), the Fondation Charles DefforeyInstitut de France and
Ligue Contre le Cancer (Equipe Labellisée). S.D. is funded by the
Agence Nationale de la Recherche. We thank the CNRS, INSERM and
Institut Curie for generous funding. The J.M research group was
supported by grants from INCa (Institut National du Cancer)
PLBIO18362 PITMM and PLBIO19 FATidique, ANR (TIESkip;
2017CE15002401), ANR18CE15001001 PLASMADIFF3D,
SIRIC Montpellier Cancer (INCa_Inserm_DGOS_12553), Labex Epi-
GenMed and Institut Universitaire de France. Work in the PP lab is
supported by grants from the Agence Nationale pour la Recherche
(ANR), Institut National du Cancer (INCa), the Ligue Nationale Contre
le Cancer (équipe labellisée) and the Fondation MSDAvenir.
Keywords: Risk Models, Chemotherapy, Aggressive Bcell non
Hodgkin lymphoma
No conflicts of interests pertinent to the abstract.
367 |SYNERGISTIC ANTICANCER EFFECT OF COMBINED
CHIDAMIDE AND ETOPOSIDE TREATMENT AGAINST NK/T CELL
LYMPHOMA
W. Song
1
, C. Shi
1
, Y. Gao
1
1
The First Affiliated Hospital of Zhengzhou University, Department of
Oncology, Zhengzhou, China
Background and purpose: Natural killer (NK)/T cell lymphoma
(NKTCL) is a highly aggressive hematological malignancy without
worldwide consensus on firstline therapy for refractory/relapsed (RR)
patients. Chidamide is a selectively histone deacetylases (HDACs) in-
hibitor. It is suggested that combined HDACs inhibitors and DNA
damaging agent can enhance anticancer effect. Etoposide is a well
known chemotherapy agent which targets type II topoisomerases,
and has been applied to treating hematological malignancies. Thus, in
this study, we investigated the synergistic anticancer effect and po-
tential mechanisms of combined chidamide and etoposide treatment in
NKTCL.
Materials and methods: A series of in vitro and in vivo experiments
were conducted using NKTCL cell lines, YT, NKYS, and KHYG1. The
inhibitory effect of chidamide or etoposide alone and their combi-
nation was detected using CCK8 assay. Cell apoptosis and cell cycle
arrest were measured using flow cytometry, morphological changes
and mitochondrial membrane potential were observed using micro-
scopy, and the expression of related proteins was examined using
western blotting. Furthermore, xenograft mouse models of NKTCL
were also established to verify the synergistic effect in vivo.
Results: We found that both chidamide and etoposide showed time
and dosedependent inhibitory effect on NKTCL cell lines, and there
remained synergism of the two drugs. Combined chidamide and
etoposide treatment significantly promoted cell apoptosis, induced
cell cycle arrest at the G2/M phase, increased histone acetylation,
decreased mitochondrial membrane potential, and caused great DNA
damage in NKTCL cell lines. In vivo, the volume and weight of the
tumor was obviously decreased due to treatment.
Conclusions: Both chidamide and etoposide inhibited the prolifera-
tion of NKTCL cell lines and showed synergistic effect in vivo and in
vitro. Combined chidamide and etoposide treatment might cause
greater DNA damage through increasing histone acetylation, arres-
ted G2/M phase, and decreasing MMP to promote apoptosis and
inhibit proliferation.
Key Words: NK/T cell lymphoma; Chidamide; Etoposide
EA previously submitted to regional or national meetings (up to
1000 attendees).
SUPPLEMENT ABSTRACTS
-
453
The research was funded by: National Science and Technology
Major Project of China (grant number 2020ZX09201009), National
Natural Science Foundation of China (grant number 81970184,
U1904139) and Department of Science & Technology of Henan
province (grant number 182102310114).
Keywords: Combination Therapies, Extranodal nonHodgkin
lymphoma
No conflicts of interests pertinent to the abstract.
368 |THE POTENTIAL EFFICACY AND MECHANISM OF
BENDAMUSTINE IN ENTRANODAL NK/T CELL LYMPHOMA
X. Feng
1
, Y. Gao
1
, H. Li
1
, M. Jin
1
, W. Song
1
, Z. Li
1
, M. Zhang
1
1
The First Affiliated Hospital of Zhengzhou University, Department of
Oncology, Zhengzhou, China
Introduction: Entranodal NK/T cell lymphoma (NKTCL) is an
aggressive malignant lymphoma, with a prevalence of East Asia.
Nowadays, despite of the promising improvement, there remains an
urgent need of novel agent to improve the dismal prognosis of
relapse and refractory patients.Bendamustine combines the proper-
ties of purine analogue and alkylating agent, which has been suc-
cessfully used for B lymphoid neoplasms. However, its use in T cell
lymphoma is limited, especially in NKTCL. Herein, we describe for the
first time the potential efficacy of bendamustine in NKTCL.
Methods and materials: NKTCL cell lines (NKYS, KHYG1, NKL) were
obtained from ExPASy. Bendamustine, chloroquine, concanamycin A
and bafilomycin were purchased from Selleckchem. Cell proliferation
was detected by CCK8. Cell apoptosis and cell cycle were detected
using commercial kit from Keygen Biotech. Antibodies used for west-
ern blot and immunofluorescence were all from Cell Signaling Tech-
nology. Nude mice were purchased from Gempharmatech and
incubated with 2*10
7
KHYG1 cells subcutaneously, then 30mg/kg
bendamustine or PBS were injected via tail vein once the tumor
appeared.
Results: Bendamustine inhibited proliferation of NKTCL cell lines in a
time and dosedependent manner. Interestingly, we noticed a syn-
ergistic effect of bendamustine with either gemcitabine or etoposide.
Mechanistically, bendamustine remarkably induced apoptosis of
NKTCL, along with upregulated cleavage of PARP, caspase3 and
caspase7, while Bcl2 was significantly downregulated. Moreover,
bendamustine induced G2/M cell cycle arrest, which was attributed
to increased pcdc2 and pcdc25c, while decreased cyclinB1. Subse-
quently, we observed significant upregulated DNA damage response
(DDR) using immunofluorescence of p‐γH2A.X after bendamustine
exposure. Meanwhile, DDR related proteins, including pATM, p
ATR, pChk1, pChk2, pP53 and p‐γH2A.X, were all increased in
both time and dosedependent way.
To further explore the mechanism of bendamustine, we pre-
treated NKTCL cell lines with autophagy and lysosomal pathway
inhibitors, and found that suppression of bendamustine on NKTLC
cells were partially abrogated. Elaborate study showed that bend-
amustine induced autophagylysosome related cell death, evidenced
by increased level of LC3II after bendamustine treatment and
further upregulated after bafilomycin treatment.
Finally, we verified effect of bendamustine on NKTCL cells in
vivo. It showed that bendamustine dramatically inhibited growth of
subcutaneous tumor, with no obvious impact on mice weight.
Conclusions: Collectively, bendamustine dramatically suppressed
NKTCL both in vitro and in vivo, most possibly caused by activated
DDR and subsequent cell apoptosis and cell cycle arrest. Autophagy
and lysosomal related cell death also contributed inhibitory effect of
bendamustine.
The research was funded by: The study was supported by the
National Natural Science Foundation of China (Grant No.82000203)
Keywords: Extranodal nonHodgkin lymphoma, Chemotherapy
No conflicts of interests pertinent to the abstract.
369 |DEEP LEARNING TO PREDICT THE EFFECT OF DRUGS IN
PATIENTS WITH LYMPHOMA BASED ON CELL LINE DATA
D. K. Chebanov
1
, I. N. Mikhaylova
2
, N. S. Tatevosova
3
1
BioAlg Corp., Research and Development, Walnut, California, USA,
2
NMRC N.N. Blokhin, Surgery 10, Moscow, Russian Federation,
3
New
York Medical College, Healthcare Organization, Valhalla, New York, USA
Patient resistance to targeted drugs, even in the presence of the
actionable biomarkers, is a significant problem, including in the
treatment of patients with lymphoma. At the same time, data from
drug testing on cell lines can help solve this problem, since machine
learning can be used to draw an analogy between the molecular
profile of a cell line and a patient's tumor.
The data were taken from the compound sensitivity data for cell
lines database Genomics of Drug Sensitivity in Cancer (GDSC), and
also gene expression profiles of the lines from Cancer Cell Line
Encyclopedia (CCLE).
First, we determined the effect of the response for cell lines in
the GDSC database: it was if the IC50 value was lower than the
maximum tested concentration.
Then we added the gene expression data from CCLE database by
merging both datasheets on cell line names. In the expression data
were selected only those most widespread genes that belong to the
cancerrelated pathways (328 genes) The resulting array consisted of
449 unique compounds and 626 cell lines, in total the datasheet had
242k rows. 94k cases has the response as effect, the rest did not
have the response. So the first step was to assess the quality of the
binary classification to predict the response to the drug. For this
purpose we calculated the sensitivity and specificity of the classifi-
cation with receiver characteristic curves (ROC) as the area under
the curve (AUC).
454
-
SUPPLEMENT ABSTRACTS
The neural network had 2 hidden layers each with 200 neurons
and was created with Keras library for python 3. The learning process
consisted of 10 epochs. We selected 90 drugs (20%) that showed
ROC AUC higher than 0.8.
On the second step we predicted the response of these drugs for
patients based on their tumor gene expression data. For that purpose
we took the patients gene expression data for the same genes from
the pancancer TCGA database, and selected only patients with the
lymphoid neoplasm diffuse large Bcell lymphoma (47 patients). Then
we used the same neural network to make the prediction.
As a result, we got the probability of the response for the drug.
For half of the drugs, no patients were found to have a response
rate greater than 70%. For the remaining drugs, the proportion of
patients for whom a greater than 70% response rate was predicted
ranged from 2 to 100%.
The high quality of prediction shows that deep learning is a
powerful tool for predicting drug response. A similar approach can
also be used for groups of drugs to predict the likelihood of inhibition
of a biological mechanism or signaling pathway. The described
method can be used to predict the results of clinical trials on patients,
to extrapolate the results of cell lines drug response to patients. With
the aim of further improvement, the list of genes for prediction will
be expanded, and feature selection techniques will be tested.
Keywords: Bioinformatics; Computational and Systems Biology Ge-
nomics, Epigenomics, and Other Omics, Risk Models
Conflicts of interests pertinent to the abstract
D. K Chebanov
Employment or leadership position: CEO
Stock ownership: Yes
370 |A PHASE 1 STUDY OF CARFILZOMIB WITH RITUXIMAB,
IFOSFAMIDE, CARBOPLATIN AND ETOPOSIDE (CRICE) IN
TRANSPLANTELIGIBLE RELAPSED/REFRACTORY DIFFUSE
LARGE BCELL LYMPHOMA
P. Torka
1
, A. Groman
2
, J. Wong
3
, B. Baysal
3
, J. Nichols
4
, A. Kader
4
,
C. Mavis
5
, S. Jani Sait
6
, A. Block
6
, E. Przespolewski
7
, A. Mohr
1
,
I. Lund
1
, K. McWhite
1
, J. Kostrewa
1
, J. DeMarco
1
, M. Johnson
1
,
A. Darrall
1
, R.N. Thomas
1
, S. Sundaram
1
, P. Ghione
1
, A. Hutson
2
,
F. HernandezIlizaliturri
1
1
Roswell Park Comprehensive Cancer Center, Medicine, Buffalo, USA,
2
Roswell Park Comprehensive Cancer Center, Biostatistics, Buffalo, USA,
3
Roswell Park Comprehensive Cancer Center, Pathology, Buffalo, USA,
4
Roswell Park Comprehensive Cancer Center, Clinical Research Services,
Buffalo, USA,
5
Roswell Park Comprehensive Cancer Center, Immunology,
Buffalo, USA,
6
Roswell Park Comprehensive Cancer Center, Cytogenetics,
Buffalo, USA,
7
Roswell Park Comprehensive Cancer Center, Pharmacy,
Buffalo, USA
Background: The CORAL study highlighted the need to develop novel
salvage regimens in R/R DLBCL previously treated with RCHOP.
Overall response rate (ORR) to second line therapy (either RICE or
RDHAP) was 51% with a 3year progression free survival (PFS) of only
30%. More recently, the SCHOLAR1 study and the antiCD19 CART
cell therapy trials have highlighted the dismal outcomes of pts with
chemorefractory disease. We previously demonstrated that 1) the
ubiquitinproteasome system (UPS) plays an important role in ac-
quired rituximabchemotherapy (RC) resistance in DLBCL and that 2)
carfilzomib (CFZ), a selective, irreversible proteasome inhibitor,
overcomes RC resistance in lymphoma preclinical models. We hy-
pothesized that targeting the UPS with CFZ could result in improved
outcomes with 2
nd
line therapy and highdose chemotherapy with
autologous stem cell transplant (HDCASCT) in R/R DLBCL pts.
Methods: We conducted a singlecenter, openlabel, prospective
phase 1 study evaluating the safety, efficacy, and pharmacokinetics/
pharmacodynamics (PK/PD) of CFZ in combination with RICE in
HDCASCT eligible R/R DLBCL pts (NCT01959698). Classic 3+3 dose
escalation schema was used to determine the MTD. Primary objec-
tives were to determine the maximum tolerated dose (MTD) and
examine the doselimiting toxicities (DLT) of CFZ in combination with
RICE. Secondary objectives include preliminary evaluation of activity,
feasibility of successful mobilization of autologous stem cells and PK/
PD analysis. Patients received CFZ (at 6 dose levels) on days 1, 2, 8, 9,
and standard doses of rituximabICE on days 36. Cycles were
repeated every 21 days for a maximum of 3 cycles before HDCASCT.
FIGURE 1 Improved PFS and OS was noted in pts with nonGCB DLBCL compared to GCB DLBCL with CRICE therapy in the R/R setting.
SUPPLEMENT ABSTRACTS
-
455
Toxicity was assessed using NCI CTCAE version 4; responses were
assessed after cycles 2 and 3 using revised Cheson criteria.
Results: In the dose escalation phase, 18 pts were enrolled at 6 dose
levels with no DLTs noted. CFZ 27 mg/m
2
was selected as the MTD.
11 additional pts were enrolled in the dose expansion phase. Median
age was 62 (2975) yrs, 55% were male, 34% had germinal center B
cell like (GCB) subtype and 62% had nonGCB subtype DLBCL by
Han's algorithm, data was missing for 1 pt. MYC and BCL2/BCL6
rearrangements were noted in 3 pts, an additional 2 pts had an iso-
lated MYC rearrangement. Best ORR was 62% (45% CR, 15% PR),
52% pts underwent HDCASCT. Interestingly, an ORR of 100% was
observed in pts with nonGCB DLBCL. Median PFS was 15.2 months
(5.1 monot reached) and median OS was NR (10.2 moNR). Pts with
nonGCB subtype had a significantly longer PFS (NR vs 7 mo, p =
0.02) and OS (NR vs 10.7 mo, p =0.002) than those with GCB
subtype (Figure 1).
Conclusion: CRICE is well tolerated in pts with R/R DLBCL with
toxicities comparable to RICE therapy. Improved outcomes observed
in nonGCB DLBCL highlight the contribution of the UPS in acquiring
rituximabchemotherapy resistance. Our data shows that pts with
nonGCB DLBCL benefit from incorporating CFZ into second line
therapy.
The research was funded by: Amgen Inc.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Chemo-
therapy, Combination Therapies
No conflicts of interests pertinent to the abstract.
371 |PRELIMINARY ACTIVITY OF DEVIMISTAT (CPI 613) IN
PATIENTS WITH RELAPSED OR REFRACTORY BURKITT
LYMPHOMA/LEUKEMIA
L. Nikolaenko
1
, T. S. Pardee
2
, R. Steiner
3
, J. S. Abramson
4
, S. Horwitz
5
,
M. Matasar
5
, C. Owens
5
, I. RodriguezRivera
5
, D. Straus
5
, S. Luther
6
,
A. Noy
5
1
City of Hope, Hematology & Hematopoietic Cell Transplantation, Duarte,
CA, USA,
2
Wake Forrest Baptist Health, Hematology, Winston Salem, NC,
USA,
3
MD Anderson Cancer Center, LymphomaMyeloma, Houston, TX,
USA,
4
Massachusetts General Hospital Cancer Center, Medicine/Lym-
phoma, Boston, MA, USA,
5
Memorial Sloan Kettering Cancer Center,
Medicine/Lymphoma, New York, USA,
6
Rafael Pharmaceuticals, Chief
Business Officer, Cranbury, NJ, USA
Introduction: Patients (pts) with primary refractory or relapsed
Burkitt lymphoma/leukemia (BL) or highgrade Bcell lymphoma with
MYC and BCL2 rearrangements (double hit, DHL) and/or BCL6 (triple
hit, THL) have a dismal prognosis. A dysregulated MYC oncogene has
downstream effects on proliferation and highly glycolytic metabolism
with tricarboxylic acid (TCA) cycle intermediates as biosynthetic
precursors. Devimistat is a nonredox active analogue of lipoic acid, a
required cofactor for two key TCA cycle mitochondrial enzymes:
pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase.
Disruption results in a shutdown of ATP and biosynthetic
intermediate production leading to cancer cell death. In a phase I
trial (n =26) a pt with multiply refractory BL had a partial remission
sustained over one year prior to resection. She remains in remission 7
years later. As of March 2021, 20 clinical studies in over 700 pts with
various cancers have been conducted (ongoing/completed) with
devimistat. We initiated a phase II trial to further explore efficacy.
Methods: NCT03793140 is a multicenter study enrolling 17 patients
on each of two cohorts BL or DHL/THL. Pts must have had one prior
therapy or are refusing standard of care, measurable disease or iso-
lated bone marrow involvement, and must not be within 3 months of a
prior stem cell transplant. Active central nervous system (CNS)
parenchymal disease is excluded, but leptomeningeal disease is
allowed if the CSF is negative for more than 4 weeks and the main-
tenance intrathecal/intraOmmaya therapy is ongoing. Devimistat is
given by central line over 2 hours daily x 5 days for two 14day cycles
and then as maintenance every 21 days. Pts are evaluable for
response if they receive at least 4/5 days of the first cycle. At least
1response in the first 9 pts by cycle 3 was needed to expand to 17 pts
in total in that cohort.
Results: 9 pts were enrolled in the DHL/THL arm. Number of prior
therapies was 3(16). No responses and only 1 stable disease resulted
in cohort closure. Thus far, 8 BL pts were enrolled. Number of prior
therapies was 3 (24). 2 pts were inevaluable. 1/6 pts had a response.
This HIV+pt had a thigh mass having received 4 prior therapies. He
had a near complete metabolic remission after 3 cycles of devimistat.
PET/CT assessment: Thigh lesion baseline October 19, 2020: 10.8 x
6.5 cm SUV 24. After cycle 3: unmeasurable, SUV 2. He is currently in
cycle 7, having had a 4week treatment delay of cycle 5 due to CoVID
19 infection. ECOG improved from 3 to 0. Adverse events (AE): As of
March 03, 2021, no serious AEs related to study drug. 4 pts had
grade 3 events at least possibly related: 2 neutropenia, 1 thrombo-
cytopenia and 1 elevated bilirubin. 1 patient had a dose reduction for
grade 2 alanine aminotransferase increase.
Conclusions: Although our results are preliminary, the near complete
remission in this patient is promising in a disease where no viable
treatment options exist.
The research was funded by: Raphael Pharmaceuticals
Keywords: Molecular Targeted Therapies, Aggressive Bcell non
Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
456
-
SUPPLEMENT ABSTRACTS
L. Nikolaenko
Research funding: Rafael
T. S Pardee
Consultant or advisory role: Rafael Pharmaceuticals
Research funding: Rafael Pharmaceuticals:
R. Steiner
Research funding: Rafael
J. S Abramson
Research funding: Rafael
M. Matasar
Consultant or advisory role: Genentech Bayer Merk Juno Thera-
peutics Roche Teva Rocket Medical Seattle Genetics Daiichi Sankyo
Takeda
Stock ownership: Merk
Honoraria: Genentech Roche GlaxoSmithKline Bayer Pharmacy-
clics Janssen Seattle Genetics Immmunovaccine Technologies Takeda
Research funding: Genentech Roche GlaxoSmithKline IGM Bio-
sciences Bayer Pharmacyclis Janssen Rocket Medical Seattle Ge-
netics Immunovaccine Technologies
S. Luther
Employment or leadership position: Rafael Pharmaceuticals
A. Noy
Consultant or advisory role: Janssen, Morphosys
Honoraria: Pharmacylics
Research funding: Raphael Pharma, Pharmacyclics, NIH
372 |PRELIMINARY SAFETY DATA FROM PATIENTS (PTS)
WITH RELAPSED/REFRACTORY (R/R) BCELL MALIGNANCIES
TREATED WITH THE NOVEL BCELL LYMPHOMA 2 (BCL2)
INHIBITOR BGB11417
C. Y. Cheah
1
, E. Verner
2
, C. S. Tam
3
, J. Hilger
4
, Y. Gao
4
, J. Huang
4
, D.
Simpson
4
, S. Opat
5
1
Sir Charles Gairdner Hospital and Pathwest Laboratory Medicine,
Nedlands; Medical School, University of Western Australia, Crawley;
Linear Clinical Research, Department of Haematology, Nedlands,
Australia,
2
Concord Repatriation General Hospital, Concord; University of
Sydney, Haematology, Sydney, Australia,
3
Peter MacCallum Cancer
Centre, Melbourne; University of Melbourne, Parkville; St Vincent's
Hospital, Fitzroy; Royal Melbourne Hospital, Haematology, Parkville,
Australia,
4
BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA,
Inc., Hematology, San Mateo, California, USA,
5
Monash Health and
Monash University, Haematology, Clayton, Australia
Background: BCL2, a key regulator of the apoptotic pathway, is
aberrantly expressed in many hematologic malignancies. Treatment
with BCL2 inhibitor venetoclax can be limited by common mild
gastrointestinal toxicities, neutropenia, and emergence of BCL2
mutations. BGB11417 was developed as a potent and highly selec-
tive inhibitor of BCL2 and has shown antitumor activity superior to
venetoclax in acute lymphoblastic leukemia, mantle cell lymphoma
(MCL), and diffuse large Bcell lymphoma (DLBCL) xenograft models.
BGB11417 has a favorable pharmacokinetic profile with low plasma
clearance in rodents and dogs. Toxicology study results have shown a
broad safety window and excellent safety profile.
Methods: BGB11417101 is a firstinhuman phase 1/1b study
(dose escalation and safety expansion) to determine safety, tolera-
bility, maximum tolerated dose (MTD), and recommended phase 2
dose of BGB11417 in pts with R/R Bcell malignancies
(NCT04277637). For dose escalation, pts were enrolled in 1 of 5 oral
BGB11417 dose levels (40, 80, 160, 320, or 640 mg once daily) and
received weekly or daily dose rampup; pts with nonHodgkin lym-
phomas (NHLs) received 2day rampup (day 1, 25% of intended
dose; day 2, 50%) before reaching the intended daily dose (day 3+,
100%). Adverse events (AEs) were reported per CTCAE v5.0. A
Bayesian logistic regression model was used to evaluate doselimiting
toxicities (DLTs; during rampup through day 21 at intended daily
dose) and determine the MTD. The first doseescalation cohort
allowed pts with R/R follicular lymphoma (FL), marginal zone lym-
phoma (MZL), DLBCL, or transformed NHL.
Results: As of 01/01/2021, 7 pts with R/R NHL had been treated. A
cohort of R/R chronic lymphocytic leukemia (CLL) had just opened
with 2 pts treated. Only data from the NHL pts are reported (5
DLBCL, 1 FL, and 1 MZL), with median followup of 2.9 mo (range,
1.77.7). The 40mg (n =3) and 80mg (n =4) dose cohorts are
complete with no DLTs. The 160mg dose cohort is underway. AEs
occurring in >1 pt are listed in Table 1. Four pts discontinued (dis-
ease progression [n =3; 2 at 40 mg, 1 at 80 mg] or lack of efficacy
[n =1 at 40 mg]), and 3 pts remain on treatment. No pt discontinued
from AEs, and no instances of laboratory or clinical tumor lysis
syndrome were observed.
Conclusion/Summary: These early phase 1 results suggest that BGB
11417 is tolerable in pts with R/R NHL at dose levels tested. Pre-
liminary activity in this pt population will be assessed with increased
enrollment and followup. Enrollment of pts with R/R CLL is un-
derway, and decreases in lymphocyte count have been seen at the
initial rampup dose of 1 mg. Evaluation of pts with MCL and Wal-
denström macroglobulinemia, and the combination of BGB11417
and Bruton tyrosine kinase inhibitor zanubrutinib, is planned for
future cohorts.
EA previously submitted to EHA 2021.
SUPPLEMENT ABSTRACTS
-
457
The research was funded by: BeiGene (Beijing) Co., Ltd., Beijing,
China and BeiGene USA, Inc., San Mateo, CA, USA
Keywords: Aggressive Bcell nonHodgkin lymphoma, Molecular
Targeted Therapies
Conflicts of interests pertinent to the abstract
C. Y. Cheah
Consultant or advisory role: Roche, Janssen, MSD, Gilead, Ascentage
Pharma, Acerta, Loxo Oncology, TG Therapeutics
Honoraria: Roche, Janssen, MSD, Gilead, Ascentage Pharma, Acerta,
Loxo Oncology, TG Therapeutics
Research funding: Celgene, Roche, AbbVie
Educational grants: Roche
E. Verner
Research funding: JanssenCilag
C. S. Tam
Honoraria: Janssen, Abbvie, Beigene
Research funding: Janssen and Abbvie
J. Hilger
Employment or leadership position: BeiGene
Stock ownership: BeiGene
Educational grants: BeiGene
Y. Gao
Employment or leadership position: BeiGene, Ltd.
Stock ownership: BeiGene, Ltd.
Educational grants: BeiGene, Ltd.
J. Huang
Employment or leadership position: BeiGene
Stock ownership: BeiGene
Educational grants: BeiGene
Other remuneration: Patents, Royalties, other Intellectual Property:
BeiGene
D. Simpson
Employment or leadership position: BeiGene
Consultant or advisory role: Abbvie, Roche Janssen
Stock ownership: BeiGene
Research funding: Roche, MSD, Acerta, Pharmacyclics, Sanofi, GCK,
Jannsen, Abbvie, Celgene, Amgen
S. Opat
Consultant or advisory role: Roche, Janssen, Abbvie, Celgene,
Takeda, Merck, Gilead, Mundipharma, AstraZeneca, CSL
Honoraria: Roche, Janssen, Abbvie, Celgene, Takeda, Merck, Gilead,
AstraZeneca
Research funding: Beigene, Roche, Janssen, Abbvie, Takeda, Merck,
Gilead, Epizyme, AstraZeneca
Educational grants: Roche
373 |PRELIMINARY CLINICAL DATA FROM A PHASE 1B
STUDY OF MAVORIXAFOR AND IBRUTINIB IN PATIENTS WITH
WALDENSTRÖM MACROGLOBULINEMIA WITH MYD88 AND
CXCR4 MUTATIONS
S. Treon
1
, C. Buske
2
, S. Thomas
3
, A. Branagan
4
, M. Dimopoulos
5
, J. J.
Castillo
1
, F. Garzon
6
, W. Tang
6
, R. Ronan
6
, S. Seyffert
6
, V. Garg
6
,
S. Ali
6
, A. Taveras
6
, A. Badarau
6
, K. Zmajkovicova
6
, S. Maier
6
,
B. Maierhofer
6
, J. Matous
7
1
Harvard Medical School, Bing Center for Waldenstrom's
Macroglobulinemia, Boston, USA,
2
University of Ulm, Comprehensive
Cancer Center and Institute of Experimental Cancer Research, Ulm,
Germany,
3
The University of Texas MD Anderson Cancer Center,
Department of Lymphoma/Myeloma, Division of Cancer Medicine,
Houston, USA,
4
Massachusetts General Hospital, Cancer Center, Boston,
USA,
5
University of Athens School of Medicine, Department of Clinical
Therapeutics, National and Kapodistrian, Athens, Greece,
6
X4
Pharmaceuticals, Boston, USA,
7
Colorado Blood Cancer Institute, Sarah
Cannon Research Institute, Denver, USA
Introduction: Waldenström macroglobulinemia (WM) is a rare dis-
order of clonal proliferation of immunoglobulin M (IgM)secreting B
cells. Most patients with WM (>90%) have somatic mutations in
MYD88. Some (40%) also have WHIMlike activating mutations in
CXCR4 (CXCR4
WHIM
) that impact response to Bruton tyrosine kinase
inhibitors (BTKi). CXC chemokine receptor type 4 (CXCR4) inhibi-
tion has been shown to sensitize CXCR4
WHIM
expressing cells to
ibrutinib. This study examines the safety and efficacy of mavorixafor,
an oral CXCR4 antagonist, in combination with ibrutinib in patients
with WM with MYD88 and CXCR4 mutations.
Methods: This phase 1b, openlabel, singlearm study
(NCT04274738) examines intrapatient dosing, safety, pharmacoki-
netics (PK), and pharmacodynamics (PD) of mavorixafor in combi-
nation with ibrutinib. Adults with clinicopathologic WM diagnosis,
consensus criteria indication for treatment, measurable disease, 3
prior therapies, and MYD88
L265P
and CXCR4
WHIM
mutations are
eligible. Patients are initiated on mavorixafor 200 mg and ibrutinib
420 mg, both oral and oncedaily (QD). Mavorixafor is escalated to
400 mg after 28 days if no doselimiting toxicities (DLTs) occur and
to 600 mg if 400 mg is deemed safe (<2/6 DLTs). Outcomes include
adverse events (AEs) and change from baseline in IgM, PK, and PD
(peripheral white blood cell [WBC] counts).
Results: At data cutoff in January 2021, 7 patients have enrolled and
remain on study. All 7 were escalated to 400 mg; 6 remain at 400 mg,
and 1 deescalated to 200 mg (median exposure, 90 days). None have
yet escalated to 600 mg. Fiftysix AEs were observed (84% grade 1).
Of 50 AEs with complete assessment for causal relationship to study
drugs, 4 were deemed related to mavorixafor only, 7 to ibrutinib only,
and 18 to the combination. One patient experienced all AEs attributed
to mavorixafor only. Only 1 DLT was observed (grade 3 hypertension
definitively related to ibrutinib and possibly related to mavorixafor).
458
-
SUPPLEMENT ABSTRACTS
No AEs led to study discontinuation, and no serious AEs were
observed. Six of 7 patients showed IgM decrease after 1 cycle. Four
patients received 3 cycles; all had IgM decrease, with 2 achieving
50% decrease consistent with partial response (median decrease,
51.0%; range, 4.4%–84.5%). Mavorixafor and ibrutinib exposures
were consistent with previous singleagent studies, and combination
treatment increased WBCs.
Conclusions: Our findings to date in patients with WM carrying
both MYD88 and CXCR4 mutations show that mavorixafor in com-
bination with ibrutinib is well tolerated at doses 400 mg QD. Un-
altered mavorixafor and ibrutinib exposures suggest no apparent
drug–drug interaction, and mavorixafor exposures tracked with
increased WBC counts. Combination of mavorixafor with ibrutinib
led to rapid and clinically meaningful decrease in IgM, suggesting
mavorixafor may sensitize CXCR4
WHIM
expressing cells to BTKi.
EA previously submitted to EHA 2021.
The research was funded by: X4 Pharmaceuticals
Keywords: Molecular Targeted Therapies, Combination Therapies,
Indolent nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
S. Treon
Consultant or advisory role: PharmaCyclics/Abbvie, Janssen Phar-
maceuticals, Beigene
Research funding: PharmaCyclics/Abbvie, Janssen Pharmaceuticals,
Beigene, BMS, Eli Lilly
C. Buske
Consultant or advisory role: Roche, Janssen, Bayer, MSD, Celltrion
Honoraria: Roche, Janssen, Bayer, MSD, Celltrion
Research funding: Roche, Janssen, Bayer, MSD, Celltrion
S. Thomas
Consultant or advisory role: Beigene, Pharmacyclics, Bristol Myers
Squibb, Ascentage Phama, Genetech, X4 Pharmaceuticals,
A. Branagan
Consultant or advisory role: Beigene, SanofiGenzyme, Karyopharm,
Pharmacyclics
M. Dimopoulos
Honoraria: AMGEN, TAKEDA, JANSSEN, BMS, BEIGENE
J. J. Castillo
Consultant or advisory role: Abbvie, Beigene, Pharmacyclics
Research funding: Abbvie, Beigene, Pharmacyclics, TG Therapeutics
F. Garzon
Consultant or advisory role: X4 Pharmaceuticals
W. Tang
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
R. Ronan
Employment or leadership position: X4 Pharmaceuticals
S. Seyffert
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals, PSU, ESPP
V. Garg
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
S. Ali
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
A. Taveras
Employment or leadership position: X4 Pharmaceuticals
A. Badarau
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
K. Zmajkovicova
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
Research funding: X4 Pharmaceuticals
S. Maier
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
Research funding: X4 Pharmaceuticals
B. Maierhofer
Employment or leadership position: X4 Pharmaceuticals
Stock ownership: X4 Pharmaceuticals
Research funding: X4 Pharmaceuticals
J. Matous
Consultant or advisory role: Janssen Pharmacyclics
374 |PHASE I STUDY OF THE CD19/CD3 HALFLIFE EXTENDED
BITE
®
MOLECULE AMG 562 IN RELAPSED/REFRACTORY DIFFUSE
LARGE B CELL LYMPHOMA, MANTLE CELL LYMPHOMA AND
FOLLICULAR LYMPHOMA
M. D. Mead
1
, L. L. Popplewell
2
, M. Subklewe
3
, A. Ghobadi
4
, J.
Kuruvilla
5
, A. Kimball
6
, C. Tuglus
7
, S. Agarwal
8
, J. Stieglmaier
9
1
Ronald Reagan UCLA Medical Center, Department of Hematology &
Oncology, Los Angeles, California, USA,
2
City of Hope National Medical
Center, Department of Hematology & Hematopoietic Cell Transplantation,
Duarte, USA,
3
LMU University Hospital Munich, Department of
Hematology & Oncology, Munich, Germany,
4
Washington University
SUPPLEMENT ABSTRACTS
-
459
School of Medicine, Division of Oncology, St. Louis, USA,
5
Princess
Margaret Cancer Centre, University of Toronto, Division of Medical
Oncology and Hematology, Toronto, Canada,
6
Amgen Inc., Oncology TA,
Clinical Research, Thousand Oaks, USA,
7
Amgen Inc., Global Biostatistical
Science, Thousand Oaks, US,
8
Amgen Inc., Clinical Pharmacology,
Modeling and Simulation, South San Francisco, USA,
9
Amgen Research
(Munich) GmbH, Early Development Hematology/Oncology, Munich,
Germany
Introduction: AMG 562, a halflife extended (HLE), BiTE
®
(bi
specific T cell engager) molecule, simultaneously engages CD19
on B cells and CD3 on T cells triggering T cellmediated serial
lysis of CD19expressing B cells. The results of a Phase I study
of AMG 562 in adult patients (pts) with relapsed or refractory
(R/R) diffuse large B cell lymphoma (DLBCL), mantle cell lym-
phoma (MCL), or follicular lymphoma (FL) are presented. The
study has since been terminated and the final results are pre-
sented here.
Methods: Safety (primary), efficacy, and pharmacokinetic (PK)
(secondary) outcomes following AMG 562 administration (IV, q1w
until disease progression, intolerance, or withdrawal of consent)
were evaluated in adults with biopsyproven DLBCL, FL, or MCL
(NCT03571828). This Phase I study was designed with an
initial dose exploration phase to be followed by a dose expansion
phase with the safety profile informing the dose for the next
cohort.
Results: At data cutoff (18 August 2020), 9 pts (DLBCL, n =4; MCL,
n=2; FL, n =3; median age, 65 [56–73] years; median prior lines of
therapy, 4 [1–15]) had received 1 dose of AMG 562 at one of two
dose levels (DL; 0.1mg, n =8; 0.3 mg, n =1).
Treatmentemergent adverse events (TEAEs) were observed in
all 9 pts and led to treatment (tx) discontinuation in 2 (both at 0.1
μg DL; pseudomonal sepsis [n =1, Gr 4], encephalopathy [n =1, Gr
4]). The encephalopathy AE was deemed to be a doselimiting
toxicity; subsequently, all subjects were premedicated with dexa-
methasone before each AMG 562 dose. No txrelated fatalities
were observed.
For most postdose time points, AMG 562 serum concentrations
were below the limit of quantification, limiting the estimation of PK
parameters. In the pt who developed encephalopathy, the end of
infusion concentration was 100fold higher relative to levels
observed in other pts.
Seven pts had progressive disease at data cutoff; response was
not assessed in 1 pt who discontinued tx. A complete metabolic
response (CMR; 2014 Lugano Classification) was noted in a 73year
old female pt with relapsed DLBCL (0.1mg DL; 5 previous lines of
therapy; ECOG status 0). CMR was characterized by disappearance
of the target lesion with no residual mass (Lugano 5point scale
score: 1) and the absence of fluorodeoxyglucose (FDG)avid focal
lesions in the bone marrow. CMR was observed by the end of cycle 1
and was maintained until the last FDGPET/CT scan before data
cutoff (cycle 6).
Conclusions: As the trial was terminated early, the limited dataset
precludes the drawing of any conclusions regarding the safety
(maximum tolerated dose/recommended Phase 2 dose) or efficacy of
AMG 562. Nevertheless, the study provides proofofconcept sup-
port for use of the HLE BiTE immunooncology platform in a variety
of hematological malignancies.
The research was funded by: Amgen Inc.
Keywords: Immunotherapy
Conflicts of interests pertinent to the abstract
L. L. Popplewell
Educational grants: Novartis
Other remuneration: Pfizer, F. HoffmannLa Roche AG
M. Subklewe
Consultant or advisory role: Amgen, BMS/Celgene, Gilead, Janssen,
Novartis, Pfizer, Seattle Genetics
Research funding: Amgen, Gilead, Miltenyi, Morphosys, Roche,
Seattle Genetics
Other remuneration: Amgen, BMS/Celgene, Gilead, Pfizer
A. Ghobadi
Consultant or advisory role: Amgen, Celgene/BMS, Kite/Gilead,
Wugen
Research funding: Kite/Gilead, Amgen
J. Kuruvilla
Consultant or advisory role: Abbvie, BMS, Gilead, Karyopharm,
Merck, Roche, Seattle Genetics
Honoraria: Amgen, Antengene, Astra Zeneca, BMS, Gilead, Incyte,
Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Ge-
netics, TG Therapeutics
Research funding: Canadian Cancer Society, Leukemia and Lym-
phoma Society Canada, Princess Margaret Cancer Foundation,
Janssen, Roche, Astra Zeneca
Other remuneration: Karyopharm (DSMB)
A. Kimball
Employment or leadership position: Amgen Inc.
Stock ownership: Amgen Inc.
C. Tuglus
Employment or leadership position: Amgen Inc.
Stock ownership: Amgen Inc.
S. Agarwal
Employment or leadership position: Amgen Inc.
Stock ownership: Amgen Inc.
J. Stieglmaier
Employment or leadership position: Amgen Research (Munich) GmbH
Stock ownership: Amgen Inc.
460
-
SUPPLEMENT ABSTRACTS
375 |PHASE I STUDY OF BENDAMUSTINE, RITUXIMAB,
IBRUTINIB, AND VENETOCLAX IN RELAPSED, REFRACTORY
MANTLE CELL LYMPHOMA
A. Kumar
1
, C. Batlevi
1
, P. Drullinsky
1
, C. Grieve
1
, L. Laraque
1
, A.
Joseph
1
, N. Mahajan
1
, M. Matasar
1
, D. Straus
1
, A. Zelenetz
1
, P.
Hamlin
1
1
Memorial Sloan Kettering Cancer Center, Medicine, New York, New York,
USA
Introduction: Bendamustine (B) and rituximab (R) with ibrutinib (IBR)
was welltolerated and efficacious (Maddocks Blood 2015). Ibrutinib
and venetoclax (VEN) were synergistic and active in relapsed, re-
fractory (R/R) MCL (Tam NEJM 2018). VEN increases apoptotic
priming and can act as a chemosensitizing agent. The aim of this phase I
study was to define the safety and tolerability of VEN with BRIBR in
R/R MCL (Clinical trial: NCT03295240).
Methods: Patients (pts) with R/R MCL received six 28day cycles of
BRIBRVEN in a 3+3 dose escalation design. Dose level 1 (DL1)
included B 90 mg/m2 day (d) 1 and 2, R 375 mg/m2 d1, and IBR
560mg daily. For cycle 1, VEN dose rampup was 20, 50, 100, and
200mg daily weekly. During cycles 26, VEN 400mg daily was given
d15. Dosing cohorts with longer duration of VEN (7d and 10d) were
planned. The study was amended to include dose level 1 (DL1) with
B at 70mg/m2, d1 and 2.
Results: As of March 2021, 7 pts were treated with BRIBRVEN
at DL1 and 3 pts at DL1. Baseline characteristics were median age
68 years (range 60 81); 90% male; 80% with Ki67 30%; 10% blastic
MCL; 40% TP53 mutant, and 100% one prior line of treatment (tx).
One dose limiting toxicity (DLT) was observed at DL1: grade 3
thrombocytopenia lasting >14 days. At DL1, 2 pts had only 5 cycles
of BRIBRVEN due to cytopenias (grade 3 neutropenia and grade 2
thrombocytopenia) despite B dose reduction. The frequent txrelated
adverse events (AEs) were thrombocytopenia (n =7), constipation
(n =6), fatigue (n =4), neutropenia (n =3), and nausea (n =4). The
grade 34 AEs were neutropenia (n =1) thrombocytopenia (n =3),
and rash (n =1). There was one txrelated serious AE: an elderly pt
was briefly hospitalized during VEN rampup for volume overload
and diuretic tx. Most pts had count recovery posttx, but one had
persistent neutropenia. Given cytopenias observed at DL1, the study
was amended to include DL1. At DL1 (n =3), there were no DLTs,
dose reductions or delays, significant cytopenias, or grade 3 tx
related AEs.
The overall response rate (ORR) was 80% (8/10), all com-
plete responses (CRs). For TP53 mutant MCL, the ORR was 50%
(2/4), all CRs. There were 5 deaths (Fig 1). Two TP53 mutant
MCL pts with primary refractory disease died of disease rapidly.
A 17p deleted MCL pt achieved a CR and underwent allogeneic
stem cell transplant and died of pneumonia (PNA) 10 mos after.
A pt in CR with posttx neutropenia died of PNA. The TP53
mutant MCL pt with a DLT after 2 cycles of BRIBRVEN
received singleagent BTKi for 27 mos until progression and
then died of COVID.
Conclusions: BRIBRVEN showed acceptable safety and tolerability
and preliminary efficacy at DL1. During the COVID pandemic,
enrollment for this immunosuppressive 4drug regimen with intrave-
nous tx was challenging. The study was closed after enrolling 3 of 6 pts
at DL1 and a definitive maximum tolerated dose was not determined.
Future study is needed to determine the role of BRIBRVEN in MCL.
The research was funded by: Genentech
Keywords: Lymphoid Cancers Other, Chemotherapy, Molecular
Targeted Therapies
Conflicts of interests pertinent to the abstract
A. Kumar
Consultant or advisory role: Kite Pharmaceuticals, Astra Zeneca, and
Celgene
FIGURE 1 Swimmer Plot for BRVEN
treated patients (n =10)
SUPPLEMENT ABSTRACTS
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461